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1.A.9 The Neurotransmitter Receptor, Cys loop, Ligand-gated Ion Channel (LIC) Family

Members of the LIC family of ionotropic neurotransmitter receptors (also called the cys-loop ligand gated ion channel family because of the signature cysteine loop in the amino terminal domain) are found in vertebrate and invertebrate animals and prokaryotes (TC# 1.A.9.8.1; Bocquet et al., 2007Sine and Engel, 2006Thompson et al., 2010). Because of the extracellular N-terminal ligand-binding domain, they exhibit receptor specificity for (1) acetylcholine (AcCh), (2) serotonin, (3) glycine, (4) glutamate and (5) γ-aminobutyric acid (GABA)in vertebrates. All of these receptor channels are hetero- or homopentameric. The best characterized are the nicotinic acetylcholine receptors (nAChRs) which are pentameric channels of α2βγδ (immature muscle) nα2βγδ (mature muscle; see 1.A.9.1.1) (Witzemann et al., 1990; Wada et al., 1998; Khiroug et al., 2002) subunit composition. All subunits are homologous and have four transmembrane α-helices, M1-M4. In all members of this family, each of the five subunits has four transmembrane alpha-helices (M1-M4) with M2 lining the pore, M1 and M3 associate with M2, and M4 is outermost and adjacent to the membrane lipids. M4 has a variety of roles: its interaction with neighboring M1 and M3 helices is important for receptor assembly, it provides transmit information on the lipid content of the membrane to the gating mechanism, it forms a vital link to the extracellular domain via the Cys-loop, and it influences channel activity (da Costa Couto et al. 2020). Sleep-related hypermotor epilepsy is associated with mutations in the alpha4beta2- nicotinic acetylcholine receptor (Weltzin et al. 2021). Signal transduction through Cys-loop receptors is mediated by the nonspecific bumping of closely apposed domains (Cymes and Grosman 2021). Howard 2021 reviewed ligand binding and gating in three model subfamilies: the prokaryotic channel GLIC, the cation-selective nicotinic acetylcholine receptor, and the anion-selective glycine receptor. Common themes include the process of capturing and annotating channels in distinct functional states with partially conserved gating mechanisms, including remodeling at the extracellular/transmembrane- domain interface; and diversity beyond the protein level, arising from posttranslational modifications, ligands, lipids, and signaling partners (Howard 2021). Peimine, an anti-inflammatory compound from chinese herbal extracts, modulates muscle-type nicotinic receptors (Alberola-Die et al. 2021). Schmauder et al. 2023 have developed methods for fast functional mapping of ligand-gated ion channels.

nAChRs are cation-selective ligand-gated ion channels exhibiting variable Ca2+ permeability depending on their subunit composition (Fucile 2017). Inhaled anesthetics alter the conformational states of LICs by binding within discrete cavities that are lined by portions of the four TMSs (Solt et al. 2006). Heusser et al. 2018 have argued in favor of a multisite model of transmembrane allosteric modulation by anesthetics, including a possible link between lipid- and receptor-based theories, that could inform the development of new anesthetics. Propofol Is an allosteric agonist with multiple binding sites on concatemeric ternary GABAA receptors (Shin et al. 2018). Alpha1beta3delta receptors may share stoichiometry and subunit arrangements with alpha1beta3gamma2 GABAA receptors (Feng and Forman 2018). 2,2,6,6-tetramethylpiperidin-4-yl heptanoate (TMPH) is a potent inhibitor of neuronal nicotinic receptors (Papke et al. 2005). Determinants of charge selectivity of the Cys-loop family of ligand-gated ion channels have been reviewed (Jensen et al. 2005).  The prokaryotic forms may function either as anion-selective or cation-selective channels, playing a role as chemotactic receptors for low molecular weight solutes (Tasneem et al. 2005). Polyunsaturated fatty acids (PUFAs) inhibit pentameric ligand-gated ion channels (pLGICs) (Dietzen et al. 2022). State-dependent inhibition of GABA receptor channels by the ectoparasiticide fluralaner has been observed (Kono et al. 2022). Potent α-conotoxin PeIA analogues with non-natural amino acids have been used for the inhibition of human α9α10 nicotinic acetylcholine receptors (Li et al. 2024).

Zn2+-activated cation channels of vertebrates and glutamate/serotonin-activated anion channels and GABA-gated cation channels of invertebrates are also in this family (Chen et al., 2006). Ligand binding has been reported to open the channel by a cis-trans prolylisomerization event (Cymeset al., 2005Lummis et al., 2005). An intra-membrane proton binding site has been linked to activation of a bacterial LIC (Wang et al., 2011). Agonists activate alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site distinct from the AcCholine site (Gill et al., 2011).  Molecular mechanisms of alcohol modulation (Rothberg 2012), desensitization (Keramidas and Lynch 2012) and assembly (Tsetlin et al., 2011) of nicotinic and other Cys-loop receptors have been reviewed.  Acidic residues on the sides of the channel mouth and in the extracellular domain play a role in cationic selectivity (Colón-Sáez and Yakel 2013). Anesthetic binding occurs in common transmembrane domains of several of the LIC recpetors (Kinde et al. 2016). Maternal taurine is a modulator of Cl- homeostasis as well as of glycine/GABA(A) receptors for neocortical development (Furukawa and Fukuda 2023). During brain and spinal cord development, GABA and glycine, the inhibitory neurotransmitters, cause depolarization instead of hyperpolarization in adults. Since glycine and GABA(A) receptors (GABA(A)Rs) are Cl- channel receptors, the conversion of GABA/glycine actions during development is influenced by changes in the transmembrane Cl- gradient, which is regulated by Cl- transporters, NKCC1 (absorption) and KCC2 (expulsion). In immature neurons, inhibitory neurotransmitters are released in a non-vesicular/non-synaptic manner, transitioning to vesicular/synaptic release as the neuron matures. The glycine/GABA system is a developmentally multimodal system that is required for neurogenesis, differentiation, migration, and synaptogenesis. Taurine cannot be synthesized by fetuses or neonates but is transferred from maternal blood through the placenta or by maternal milk ingestion. In the developing neocortex, taurine levels are higher than GABA levels, and taurine tonically activates GABA(A)Rs to control radial migration as a stop signal. In the marginal zone (MZ) of the developing neocortex, endogenous taurine modulates the spread of excitatory synaptic transmission, activating glycine receptors (GlyRs) as an endogenous agonist. Thus, taurine affects information processing and crucial developmental processes such as axonal growth, cell migration, and lamination in the developing cerebral cortex (Furukawa and Fukuda 2023). 

Function based analysis of major biological pathways and mechanisms associated with schizophrenia (SCZ) genes identified glutaminergic receptors (e.g., GRIA1, GRIN2, GRIK4, GRM5), serotonergic receptors (e.g., HTR2A, HTR2C), GABAergic receptors (e.g., GABRA1, GABRB2), dopaminergic receptors (e.g., DRD1, DRD2), calcium-related channels (e.g., CACNA1H, CACNA1B), and solute transporters (e.g., SLC1A1, SLC6A2) (Sundararajan et al. 2018). Others are involved in neurodevelopment (e.g., ADCY1, MEF2C, NOTCH2, SHANK3). Biological mechanisms involving synaptic transmission, regulation of the membrane potential and transmembrane ion transport were identified as leading molecular functions associated with SCZ genes (Sundararajan et al. 2018). Antagonism of alpha4beta2 nicotinic acetylcholine receptors has been shown by fluoroquinolone antibiotics (Sanders et al. 2022). LiGIoNs is a profile Hidden Markov Model (pHMM) method for the prediction and ligand-based classification of LGICs (Apostolakou et al. 2022). The method consists of a library of 10 pHMMs, one per LGIC subfamily, built from the alignment of representative LGIC sequences. In addition, 14 Pfam pHMMs are used to further annotate and classify unknown protein sequences into one of the 10 LGIC subfamilies ((Apostolakou et al. 2022)).

The 5-HT(3) and acetylcholine receptors (cationic ion channels) and the GABA(A) and glycine receptors (anionic ion channels) generally depolarize or hyperpolarize, respectively, the neuronal membrane. Within the amino-terminal extracellular region, all members of this family exhibit a similar architecture of ligand binding domains, and a number of key residues are completely conserved (Connolly, 2008). Zhu and Hummer (2009) have concluded that the conformational transition from open and closed states involves no major rotations of the transmembrane helices, and is instead characterized by a concerted tilting of helices M2 and M3. In addition, helix M2 changes its bending state, which results in an early closure of the pore during the open-to-closed transition. N-alcohols potential H+-activated LIC currents in prokaryotes and eukaryotes (including glycine, GABA and acetylcholine receptors) (Howard et al., 2011). Insecticides targeting pentameric ligand-gated channels are structural mimetics of neurotransmitters or manipulate and deregulate the proteins (Raisch and Raunser 2023). Those binding to (pseudo-)tetrameric voltage-gated(-like) channels are natural or synthetic compounds that directly block the ion-conducting pore or prevent conformational changes in the transmembrane domain necessary for opening and closing the pore (Raisch and Raunser 2023).

The three-dimensional structures of the protein complex in both the open and closed configurations have been solved (Miyazawa and Unwin, 2003Baenziger and Corringer, 2011). The five subunits (each of 400-500 amino acyl residues in length) are arranged in a ring with their 'M2' transmembrane helical spanners lining the central channel. The five M2 segments come together in the middle of the membrane to form the channel gate, and the gate opens upon binding of acetylcholine to distant sites in the N-terminal domains of the two α-subunits. The M2 segment determines the anion versus cation selectivity (Menard et al., 2005). These general structural features are probably valid for all members of the family. The acetylcholine receptor subunit consists of two domains, the channel domain and the ligand-binding extracellular domain. The latter is homologous to a soluble protein, the acetylcholine binding protein (AChBP), the structure of which has been solved at high resolution (Brejc et al., 2001). Nicotine interacts with nicotinic acetylcholine receptors and decreases food intake through activation of POMC neruons (Mineur et al. 2011). An intrasubunit nicotinic acetylcholine receptor binding site for the positive allosteric modulator Br-PBTC has been identified (Norleans et al. 2019). The nAChR adopts different conformations and locates in distinct lipid domains, dependent on the lipid composition of the membane, and this has a direct effect on its function (Fabiani et al. 2022).

Pentameric ligand-gated ion channels of the Cys-loop family mediate fast chemo-electrical transduction. Bocquet et al., 2009 presented the X-ray structure at 2.9 A resolution of the bacterial Gloeobacter violaceus pentameric ligand-gated ion channel homologue (GLIC) at pH 4.6 in an apparently open conformation. This cationic channel is permanently activated by protons. The structure is arranged as a funnel-shaped transmembrane pore widely open on the outer side and lined by hydrophobic residues. On the inner side, a 5 A constriction matches with rings of hydrophilic residues that are likely to contribute to the ionic selectivity. Structural comparison with ELIC, a bacterial homologue from Erwinia chrysanthemi solved in a presumed closed conformation (TC #1.A.9.9.1), shows a wider pore where the narrow hydrophobic constriction found in ELIC is removed. Comparative analyses of GLIC and ELIC revealed, in concert, a rotation of each extracellular beta-sandwich domain as a rigid body, interface rearrangements, and a reorganization of the transmembrane domain, involving a tilt of the M2 and M3 alpha-helices away from the pore axis. These data are consistent with a model of pore opening based on both quaternary twist and tertiary deformation (Bocquet et al., 2009).

According to Miyazawa et al. (2003), the pore is shaped by the inner ring of 5 α-helices, which curve radially to create a tapering path for the ions, and an outer ring of 15 α-helices, which coil around each other and shield the inner ring from the lipids. The gate is a constricting hydrophobic girdle at the middle of the lipid bilayer, formed by weak interactions between neighboring inner helices. When acetylcholine enters the ligand-binding domain, it triggers rotations of the protein chains on opposite sides of the entrance to the pore. These rotations are communicated through the inner helices, and open the pore by breaking the girdle apart (Miyazawa et al., 2003). (Nury et al., 2010) have presented a microsecond molecular dynamics simulation of channel gating in a nicotinic receptor homologue.

Bouzat et al. (2004) have identified structural requirements for functionally coupling the AcCh binding domain to the pore-forming domain. At least three loops in the AcCh binding domain interact with the pore domain to trigger channel opening. Modeling suggests a network of interacting loops between the two domains mediate allosteric coupling (Bouzat et al., 2004). Acetylcholine receptor channel gating is a brownian conformational cascade in which nanometer-sized domains ('Phi blocks') move in staggering sequence to link an affinity change at the transmitter binding sites with a conductance change in the pore. In the alpha-subunit, the first Phi-block to move during channel opening, is comprised of residues near the transmitter binding site, and the second is comprised of residues near the base of the extracellular domain (Purohit and Auerbach, 2007).

Muscle contraction is triggered by the opening of acetylcholine receptors at the vertebrate nerve-muscle synapse. The M2 helix of this allosteric membrane protein lines the channel, and contains a 'gate' that regulates the flow of ions through the pore. Single-molecule kinetic analysis has been used to probe the transition state of the gating conformational change and estimate the relative timing of M2 motions in the α-subunit of the murine acetylcholine receptor (Purohitet al., 2007). αM2 move in three discrete steps. The core of the channel serves both as a gate that regulates ion flow and as a hub that directs the propagation of the gating isomerization through the membrane domain of the acetylcholine receptor.

GABA interacts with three kinds of receptors, classes A, B and C. Classes A and C receptors are ligand-gated Cl- channels while class B receptors activate other channels via G proteins. GABA binding to both Class A and C receptors opens the Cl- channels, leading to increased membrane conductance. These two classes of receptors differ in their antagonist specificities and therefore are distinguished pharmacologically. These receptors consist of 6 types of subunits: α, β, γ, δ, ε, and π. There are 6 αs, 3 βs and 3 γs, and 1 each of the δ, ε and π subunits. Usually the pentamer consists of 2αs, 2 βs and 1 γ, each with 4 putative TMSs, a long N-terminus and a short C-terminus, both extracellular. These receptors possess binding sites for anti-epileptic drugs, sedatives and anesthetics. Evidence suggests that the TMS1-2 hairpin loops of the 5 subunits comprise the GABA receptor pore (Filippova et al., 2004).  GABA type A receptors, the brain's major inhibitory neurotransmitter receptors, are the targets for many general anesthetics, including volatile anesthetics, etomidate, propofol, and barbiturates.  They bind at intersubunit sites (Chiara et al. 2013). Biophysical properties of alpha1beta2 and alpha3beta2 GABAA receptors in whole-cell patch-clamp electrophysiological recordings have been characterized and compared (Olander et al. 2020).

γ-Aminobutyric acid type A (GABAA) receptors consist of subunits whose assembly forms a neurotransmitter-gated anion channel. Subunits for this receptor constitute a large family whose members are classified according to primary structure as α, β, γ, and δ, ε, π, and ρ subunits. Recombinant expression studies of different α variants in combination with a β variant and the γ2 subunit demonstrated that GABAA receptors with distinct pharmacological properties are generated. A distinctive mark of these αxβxγ2 receptors is their ability to bind modulatory compounds such as benzodiazepines (BZs), which can modulate γ-aminobutyric acid (GABA)-gated channel activity at an allosteric site. The α variants determine the affinity of GABAA receptor subtypes toward these modulatory compounds, and members of the γ-subunit class, in particular, the γ2 variant, are essential for the architecture of the BZ site. Furthermore, the γ subunits impart a large unitary conductance on GABAA channels (Herb et al., 1992). N

Nineteen GABAAR subunits had been identified and categorized into eight classes by 2018,, alpha1-6, beta1-3, gamma1-3, delta, epsilon, theta, pi and rho1-3, but their variety is further broadened by the existence of several splice forms for certain subunits (e.g., alpha6, beta2 and gamma2) (Has and Chebib 2018). The subunits within each class have an aa sequence identiy of 70% or more, whereas those with a sequence identity of 30% or less are grouped into different classes. There is a wide range of subunit combinations (Has and Chebib 2018).

The endocannabinoid system is a lipid signaling network that modulates different brain functions. Sigel et al. (2011) showed a direct molecular interaction between the two systems. The endocannabinoid 2-arachidonoyl glycerol (2-AG) potentiates GABA(A) receptors at low concentrations of GABA. Two residues of the receptor located in the transmembrane segment M4 of β(2) confer 2-AG binding. 2-AG acts in a superadditive fashion with the neurosteroid 3α, 21-dihydroxy-5α-pregnan-20-one (THDOC) and modulates δ-subunit-containing receptors, known to be located extrasynaptically and to respond to neurosteroids. 2-AG inhibits motility in CB(1)/CB(2) cannabinoid receptor double-KO, whereas β(2)-KO mice show hypermotility. The identification of a functional binding site for 2-AG in the GABA(A) receptor may have far-reaching consequences for the study of locomotion and sedation (Sigel et al., 2011).

γ-aminobutyric type A (GABAA ) receptors are the main inhibitory neurotransmitter receptors in the brain and are targets for numerous clinically important drugs such as benzodiazepines, anxiolytics, and anesthetics. Pyrazoloquinoline 2-p-methoxyphenylpyrazolo [4,3-c] quinolin-3(5H)-one (CGS 9895) is a positive allosteric modulator acting through the alpha+/beta- interface in the extracellular domain of GABAA receptors. The alpha1 Y209 residue present at the extracellular alpha+/beta- subunit interface is a key residue for the positive allosteric modulation of the GABAA receptor by CGS 9895 (Maldifassi et al. 2016). Neurosteroid inhibitors such as pregnenolone sulphate bind from the lipid bilayer to sites that are distinct from those of the GABA channel blocker picrotoxinin, and different GABAARs are differentially affected by these inhibitors (Seljeset et al. 2018).

γ2 and δ subunits share approximately 35% sequence identity with α and β subunits and form functional GABA-gated chloride channels when expressed alone in vitro. The γ2 subunit is the rat homologue of the human γ2 subunit shown to be important for benzodiazepine pharmacology (Shivers et al., 1989). Functional GABA receptors mediating Cl- uptake in a picrotoxin-sensitive process (α5, β1, γ1) have been identified and shown to be functional in renal proximal tubular cells (Sarang et al., 2008).

A novel type of GABA receptor has been characterized (Beg and Jorgensen, 2003). It is an excitatory GABA gated cation channel (TC #1.A.9.7.1). This channel is the EXP-1 receptor of the nematode, C. elegans. It is as divergent in sequence from the A and C class anion selective GABA receptors as it is from the other ligand-gated ion channel proteins in TCDB. It therefore represents a new subfamily in the LIC family. Inhibitory glycine receptors (GlyR) mediate Cl- influx and bind strychnine with nanomolar affinity. They are present in various nervous tissues (spinal cord, brain stem, caudal brain and retina (Cascio, 2004). Reduced activities of mutants often results in channelopathies involving muscle tone regulation including human startle disease (hyperekplexia). There are multiple subunit subtypes in humans (α1, α2, α3, α4 and β subunits) (Cascio, 2004)). Alternative splicing also occurs. In adults, the most common pentameric form consists of α1and β subunits. The M2α-helix region peptide of α1 GlyR in lipid vesicles forms chloride-conducting pores, and sympathetic M2-based peptides form Cl- channels in cell membranes (Mitchell et al., 2000).

There are seven classes of serotonin (5 hydroxytryptamine (5HT) receptors, six of which are G-protein linked, plus one of which is a homo- or heteropentameric ligand gated non-specific cation channel (TC #1.A.9.2.1 and 2) of the LIC family (Reeves and Lummis, 2002). Anion selective serotonin receptors may be present in C. elegans (TC #1.A.9.6.1). As for other LIC family members, four transmembrane hydrophobic segments (TMSs) (M1-M4) are predicted by hydropathy analysis.

The neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] mediates rapid excitatory responses in peripheral and central neurons by activating ligand-gated ion channels (5-HT3 receptors). These receptors are expressed in a variety of peripheral ganglia, where they are thought to modulate responses to pain, and to control reflexes of the enteric and cardiovascular systems. In the central nervous system, 5-HT3 receptors have been implicated in the control of emesis, and antagonists of 5-HT3 receptors have found clinical use for suppression of the nausea that accompanies postoperative recovery and many cancer therapies. Most families of ligand-gated ion channels are composed of multiple subunit types that assemble in alternative combinations to achieve functional diversity (Hanna et al., 2000).

Recombinant expression of 5-HT3A subunits alone yields functional 5-HT3receptors, but, heteromeric assemblies of the human 5-HT3A and 5-HT3B subunits more closely resemble native 5-HT3 receptors of rodent ganglia with respect to their single-channel conductance and permeability to Ca2+ ions. Consequently, it is likely that rodent ganglia normally express heteromeric 5-HT3 receptors. However, the 5-HT3 receptors of different species display several distinctive properties, particularly with respect to their pharmacological profiles (Hanna et al., 2000).

The channel protein complexes of the LIC family preferentially transport cations or anions depending on the channel (e.g., the acetylcholine and serotonin receptors are cation-selective while glycine receptors are anion-selective). α1β heteromeric receptors are likely to be the predominant synaptic form of glycine receptors in adult mammals. (Burzomato et al., 2004). Glycine binding increases Cl-conductance producing superpolarization and inhibition of neuronal firing. Gephyrin (Q9NQX3) anchors glycine receptors to subsynaptic microtubules.

Several homologous bacterial LIC family members have been identified (eg, 1.A.9.8-9) Hilf and Dutzler (2008) have presented X-ray structures of a pentameric ligand-gated ion channel from the bacterium Erwinia chrysanthemi at 3.3 A resolution. This high resolution structure provides a model system for the investigation of the general mechanisms of ion permeation and gating within the LIC family.

Pentameric ligand-gated ion channels (LGICs) are fast-gating receptors, represented by cationic nicotinic acetylcholine (nAChR) and serotonin (5HT3R) receptors, and by anionic GABA and glycine (GlyR) receptors. Because of a highly conserved sequence of 13 amino acids flanked by two canonical cysteine residues shared by all members of the family, these receptors are also known as the Cys-loop family. These receptors are allosteric transmembrane proteins made of five identical or non-identical subunits arranged (pseudo) symmetrically around a central ion pore in the membrane. In nAChR, upon ACh binding, the receptor interconverts into discrete allosteric states, with each state corresponding to a different physiological state: resting (closed), active (open), and desensitized (closed) (Grutter et al. 2006). The intracellular domain of homomeric glycine receptors modulates agonist efficacy (Ivica et al. 2020).

The inhibitory glycine receptor is a ligand-gated ion channel with a pentameric assembly from ligand binding alpha and structural beta subunits. In addition to alpha subunit gene variants (alpha1-alpha4) and developmental alterations in subunit composition of the receptor protein complex, alternative splicing of both alpha and beta subunits has been found to contribute to glycine receptor heterogeneity (Oertel et al. 2007).

Ca2+ permeability is determined by charged amino acids at the extracellular end of the M2 transmembrane domain, which could form a ring of amino acids at the outer end of the cation channel. Alpha4, alpha5, and beta3 subunits all have a homologous glutamate in M2 that contributes to high Ca2+ permeability, whereas beta2 has a lysine at this position. Subunit combinations or single amino acids changes at this ring that have all negative charges or a mixture of positively and negatively charged amino acids are permeable to Ca2+. All positive charges in the ring prevent Ca2+ permeability. Increasing the proportion of negative charges is associated with increasing permeability to Ca2+ (Tapia et al. 2007).

Hibbs and Gouaux (2011) presented the three-dimensional structure of an inhibitory anion-selective Cys-loop receptor, the homopentameric Caenorhabditis elegans glutamate-gated chloride channel α (GluCl), at 3.3 Å resolution. The structures were determined with the allosteric agonist ivermectin (PDB#3RIF), the neurotransmitter L-glutamate and the open-channel blocker picrotoxin. Ivermectin, used to treat river blindness, binds in the transmembrane domain of the receptor and stabilizes an open-pore conformation. Glutamate binds in the classical agonist site at subunit interfaces, and picrotoxin directly occludes the pore near its cytosolic base. GluCl provides a framework for understanding mechanisms of fast inhibitory neurotransmission and allosteric modulation of Cys-loop receptors in general.

Cys loop, glutamate, and P2X receptors are ligand-gated ion channels (LGICs) with 5, 4, and 3 protomers, respectively. Agonists and competitive antagonists apparently induce opposite motions of the binding pocket (Du et al., 2012). Agonists, usually small, induce closure of the binding pocket, leading to opening of the channel pore, whereas antagonists, usually large, induce opening of the binding pocket, thereby stabilizing the closed pore.

Using crosstalk between the nicotinic acetylcholine receptor (nAChR) and its lipid microenvironment, structural motifs that are conserved within the nAChR family, contemporary eukaryotic members of the pentameric ligand-gated ion channel (pLGIC) superfamily, and also bacterial homologues have been analyzed. The evolutionarily conserved design is manifested in: 1) the concentric three-ring architecture of the transmembrane region, 2) the occurrence in this region of distinct lipid consensus motifs in prokaryotic and eukaryotic pLGIC and 3) the key participation of the outer TMS4 ring in conveying the influence of the lipid membrane environment to the middle TMS1-TMS3 ring and this, in turn, to the inner TMS2 channel-lining ring, which determines ion selectivity. 

LICs or pLGICs have the same overall structure but with different combinations of agonist specificities and permeant ion charge selectivities. Three distantly related cation-selective members, the mouse muscle nicotinic acetylcholine receptor (nAChR), and the bacterial GLIC and ELIC channels, have differing sensitivities to TMA+ and TEA+ which block the nAChR and GLIC but not ELIC at low concentrations which transports both cations. Lidocaine binding speeds up the current-decay time courses of nAChR and GLIC in the presence of saturating concentrations of agonists, but its binding to ELIC slows this time course. Thus, one can not generalize results obtained with one channel to others (Gonzalez-Gutierrez and Grosman 2015). 

Acetylcholine binds in the nAChR extracellular domain at the interface between two subunits and a large number of nAChR-selective ligands, including agonists and competitive antagonists, that bind at the same site are known. More recently, ligands that modulate nAChR function by binding to sites located in the transmembrane domain have been studied. These include positive allosteric modulators (PAMs), negative allosteric modulators (NAMs), silent allosteric modulators (SAMs) and compounds that are able to activate nAChRs via an allosteric binding site (allosteric agonists) (Chatzidaki and Millar 2015).

The amine-gated Erwinia chrysanthemi LIC is activated by primary amines, while the transmembrane domain of the Gloeobacter violaceus LIC is activated by protons. Schmandt et al. 2015 found that a chimera was independently gated by primary amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines revealed a closed-pore conformation and an C-terminal domain that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes  showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels.

Cys-loop receptors have structural elements that are well conserved with a large extracellular domain (ECD) harboring an alpha-helix and 10 beta-sheets. Following the ECD, four transmembrane domains (TMD) are connected by intracellular and extracellular loop structures (Langlhofer and Villmann 2016). Except the TMS 3-4 loop, their lengths are only 7-14 residues. The TMS 3-4 loop forms the largest part of the intracellular domain (ICD) and exhibits the most variable region between all of these homologous receptors. The ICD is defined by the TMS 3-4 loop together with the TMS 1-2 loop preceding the ion channel pore (Langlhofer and Villmann 2016). Crystallization has revealed structures for some members of the CLR family, but to allow crystallization, the intracellular loop was usually replaced by a short linker present in prokaryotic CLRs, so their structures as not known. Nevertheless, this intracellular loop appears to function in desensitization, modulation of channel physiology by pharmacological substances, and posttranslational modifications.  Motifs important for trafficking are therein, and the ICD interacts with scaffold proteins enabling inhibitory synapse formation (Langlhofer and Villmann 2016). 

Ivermectin (IVM) is a widely used antiparasitic drug in humans and pets which activates glutamate-gated Cl- channels in parasites. It is known that IVM binds to the transmembrane domains of several ligand-gated channels, such as Cys-loop receptors and P2X receptors. Chen et al. 2017 found that the G-protein-gated inwardly rectifying K+ (GIRK) channel is also activated by IVM directly.

Neurosteroids are endogenous sterols that potentiate or inhibit pentameric ligand gated ion channels and can be effective anesthetics, analgesics, or anti-epileptic drugs. The complex effects of neurosteroids suggest the presence of multiple binding sites in these receptors. This has been demonstrated using GLIC (TC# 1.A.9.8.1) as the target channel protein (Cheng et al. 2018).

GABA(A) receptors are ligand-gated ion channels consisting of five subunits from eight subfamilies, each assembled in four hydrophobic transmembrane domains. This pentameric structure not only allows different receptor binding sites, but also various types of ligands, such as orthosteric agonists and antagonists, positive and negative allosteric modulators, and second-order modulators and non-competitive channel blockers. There are both synthetic and natural GABA(A)-receptor modulators. Çiçek 2018 reviewed natural GABA(A)-receptor modulators and discussed their structure-activity relationships. 

Cell surface expression of type-A GABA receptors (GABAARs) is a critical determinant of the efficacyfor inhibitory neurotransmission. Pentameric GABAARs are assembled from a large pool of subunits according to precise co-assembly rules that limit the extent of receptor structural diversity. These rules ensure that particular subunits, such as rho1 and beta3, form functional cell surface ion channels when expressed alone in heterologous systems, whereas other brain-abundant subunits, such as alpha and gamma, are retained within intracellular compartments. Normally, surface expression of alpha and gamma subunits requires co-assembly with beta subunits via interactions between their N-terminal sequences in the endoplasmic reticulum. Hannan and Smart 2018 identified two residues in the transmembrane domains of alpha and gamma subunits, which, when substituted for their rho1 counterparts, permit cell surface expression as homomers. Consistent with this, substitution of the rho1 transmembrane residues for the alpha-subunit equivalents reduced surface expression and altered channel gating, highlighting their importance for GABAAR trafficking and signaling. Although not ligand-gated, alpha and gamma homomeric ion channels were functional at the cell surface (Hannan and Smart 2018). 

The protein has two cholesterol binding sites: an intersubunit site between TM3 and TM1 of adjacent subunits and an intrasubunit site between TM1 and TM4. In both sites, cholesterol is oriented such that the 3OH group points toward the center of the transmembrane domains rather than toward either the cytosolic or extracellular surfaces(Budelier et al. 2019). Allopregnanolone, a neurosteroid that allosterically modulates pLGICs, binds to the same binding pockets although the binding orientations of the two ligands were different, with the 3OH group of allopregnanolone pointing to the intra- and extracellular termini of the TMSs rather than to their centers. Cholesterol increases, whereas allopregnanolone decreases the thermal stability of GLIC. Thus, cholesterol and neurosteroids bind to common hydrophobic pockets in GLIC, but their effects depend on the orientation and specific molecular interactions unique to each sterol. I

Ionized side chains - whether pore-facing or buried - in the first α-helical turn of the second TMS determines charge discrimination in the substrate ion. However, electrostatics of backbone atoms are not critically involved. On the basis of electrophysiological observations, not only the sign of charged side chains but also their conformations seem to be crucial determinants of cation-anion selectivity.  Thus, side-chain conformation is important for charge selectivity in Cys-loop receptors (Harpole and Grosman 2019).

At nM concentration, APPsα is an allosteric activator of α7-nAChR, mediated by C-terminal 16 amino acids (CTα16) (Korte 2019). At µM concentrations, Rice et al. 2019 identified the GABABR1a as a target of APPsα, binding the sushi 1 domain via a 17–amino acid sequence (17-mer). These receptors activate opposing downstream cascades.

CLIC from a Desulfofustis deltaproteobacterium (TC# 1.A.9.9.3), the x-ray structure of which has been determined, includes a periplasmic NTD fused to the conventional ligand-binding domain (LBD) (Hu et al. 2020). The NTD consists of two jelly-roll domains interacting across each subunit interface. Binding of Ca2+ at the LBD subunit interface is associated with a closed transmembrane pore, with resolved monovalent cations intracellular to the hydrophobic gate. Accordingly, DeCLIC-injected oocytes conducted currents only upon depletion of extracellular Ca2+. DeCLIC crystallized in the absence of Ca2+ with a wide-open pore and remodeled periplasmic domains, including increased contacts between the NTD and classic LBD agonist-binding sites. Functional, structural, and dynamical properties of DeCLIC paralleled those of sTeLIC, a pLGIC from another symbiotic prokaryote. Based on these DeCLIC structures, the previous structure of bacterial ELIC (the first high-resolution structure of a pLGIC) should be reclassified as a 'locally closed' conformation. Structures of DeCLIC in multiple conformations illustrate dramatic conformational state transitions and diverse regulatory mechanisms available to ion channels in pLGICs, particularly involving Ca2+ modulation and periplasmic NTDs (Hu et al. 2020).

Most general anaesthetics and classical benzodiazepine drugs act through positive modulation of gamma-aminobutyric acid type A (GABAA) receptors to dampen neuronal activity in the brain. Kim et al. 2020 presented cryo-EM structures of GABAA receptors bound to intravenous anaesthetics, benzodiazepines and inhibitory modulators in a lipidic environment. Structures of GABAA receptors in complex with the anaesthetics, phenobarbital, etomidate and propofol, reveal both distinct and common transmembrane binding sites, which are shared in part by the benzodiazepine drug diazepam. Structures in which GABAA receptors are bound by benzodiazepine-site ligands identify an additional membrane binding site for diazepam and suggest an allosteric mechanism for anaesthetic reversal by flumazenil (Kim et al. 2020).

GABAA receptors are a major contributor to fast inhibitory neurotransmission in the brain. These receptors are activated upon binding the transmitter GABA or allosteric agonists including a number of GABAergic anesthetics and neurosteroids. Functional receptors can be formed by various combinations of the nineteen GABAA subunits cloned to date. GABAA receptors containing the epsilon subunit exhibit a degree of constitutive activity. Germann et al. 2022 have characterized the functional properties of the rat α1β2ε GABAA receptor which exhibits a higher level of constitutive activity than typical of GABAA receptors, but it is inefficaciously activated by the transmitter and the allosteric agonists propofol, pentobarbital, and allopregnanolone. 

The reaction catalyzed by LIC family members is:

ions (in) ↔ ions (out)

References associated with 1.A.9 family:

and Franks NP. (2015). Structural comparisons of ligand-gated ion channels in open, closed, and desensitized states identify a novel propofol-binding site on mammalian gamma-aminobutyric acid type A receptors. Anesthesiology. 122(4):787-94. 25575161
and Rothberg BS. (2012). The BK channel: a vital link between cellular calcium and electrical signaling. Protein Cell. 3(12):883-92. 22996175
Abad, I.P.L., R.L. Fam, D.T. Nguyen, C.J. Nowell, P.N.H. Trinh, D.T. Manallack, L.A. Freihat, J. Chakrabarti, A. Jamil, B. Exintaris, N.S. Yaakob, and H.R. Irving. (2020). Visualising functional 5-HT receptors containing A and C subunits at or near the cell surface. Biomed Pharmacother 132: 110860. 33059258
Aboheimed, G.I., M.M. AlRasheed, S. Almudimeegh, K.A. Peña-Guerra, K.J. Cardona-Londoño, M.A. Salih, M.Z. Seidahmed, F. Al-Mohanna, D. Colak, R.J. Harvey, K. Harvey, S.T. Arold, N. Kaya, and A.J. Ruiz. (2022). Clinical, genetic, and functional characterization of the glycine receptor β-subunit A455P variant in a family affected by hyperekplexia syndrome. J. Biol. Chem. 298: 102018. 35526563
Absalom, N.L., P.K. Ahring, V.M. Liao, T. Balle, T. Jiang, L.L. Anderson, J.C. Arnold, I.S. McGregor, M.T. Bowen, and M. Chebib. (2019). Functional genomics of epilepsy-associated mutations in the GABA receptor subunits reveal that one mutation impairs function and two are catastrophic. J. Biol. Chem. [Epub: Ahead of Print] 30728247
Al Rawashdah, S., A. Hamrouni, B. Sadek, R. Amer, M. Metwaly, N. Atatreh, and M.A. Ghattas. (2019). Molecular modelling studies on ɑ7 nicotinic receptor allosteric modulators yields novel filter-based virtual screening protocol. J Mol Graph Model 92: 44-54. 31306865
Alberola-Die, A., G. Fernández-Ballester, J.M. González-Ros, I. Ivorra, and A. Morales. (2016). Muscle-Type Nicotinic Receptor Modulation by 2,6-Dimethylaniline, a Molecule Resembling the Hydrophobic Moiety of Lidocaine. Front Mol Neurosci 9: 127. 27932949
Alberola-Die, A., J.A. Encinar, R. Cobo, G. Fernández-Ballester, J.M. González-Ros, I. Ivorra, and A. Morales. (2021). Peimine, an Anti-Inflammatory Compound from Chinese Herbal Extracts, Modulates Muscle-Type Nicotinic Receptors. Int J Mol Sci 22:. 34681946
Alexander, S.P.H. and J.A. Peters. (1997). Receptor and ion channel nomenclature supplement. Trends Pharmacol. Sci. 18: 4-6; 36-40; 42-44.
Alldred, M.J., J. Mulder-Rosi, S.E. Lingenfelter, G. Chen, and B. Lüscher. (2005). Distinct gamma2 subunit domains mediate clustering and synaptic function of postsynaptic GABAA receptors and gephyrin. J. Neurosci. 25: 594-603. 15659595
Althoff, T., R.E. Hibbs, S. Banerjee, and E. Gouaux. (2014). X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors. Nature 512: 333-337. 25143115
Alvarez, L.D. and A. Pecci. (2018). Structure and dynamics of neurosteroid binding to the αβγ GABA receptor. J Steroid Biochem Mol Biol. [Epub: Ahead of Print] 29705269
Alvarez, L.D. and A. Pecci. (2019). Mapping the neurosteroid binding sites on glycine receptors. J Steroid Biochem Mol Biol 192: 105388. 31176751
Alvarez, L.D. and N.R.C. Alves. (2022). Molecular determinants of tetrahydrocannabinol binding to the glycine receptor. Proteins. [Epub: Ahead of Print] 36271319
Alvarez, L.D., A. Pecci, and D.A. Estrin. (2019). In Search of GABA Receptor''s Neurosteroid Binding Sites. J Med Chem 62: 5250-5260. 30566352
Amanzougaghene, N., F. Fenollar, G. Diatta, C. Sokhna, D. Raoult, and O. Mediannikov. (2018). Mutations in GluCl associated with field ivermectin-resistant head lice from Senegal. Int J Antimicrob Agents 52: 593-598. 30055248
Amundarain, M.J., J.F. Viso, F. Zamarreño, A. Giorgetti, and M. Costabel. (2018). Orthosteric and benzodiazepine cavities of the αβγ GABA receptor: insights from experimentally validated in silico methods. J Biomol Struct Dyn 1-19. [Epub: Ahead of Print] 29633901
Antović, A., R. Karadžić, J. Živković, and A. Veselinovic. (2023). Development of QSAR model based on Monte Carlo optimization for predicting GABAA receptor binding of newly emerging benzodiazepines. Acta Chim Slov 70: 634-641. 38124634
Apostolakou, A.E., K.C. Nastou, G.N. Petichakis, Z.I. Litou, and V.A. Iconomidou. (2022). LiGIoNs: A computational method for the detection and classification of ligand-gated ion channels. Biochim. Biophys. Acta. Biomembr 1864: 183956. 35577076
Arcario, M.J., C.G. Mayne, and E. Tajkhorshid. (2017). A membrane-embedded pathway delivers general anesthetics to two interacting binding sites in the Gloeobacter violaceus Ion Channel. J. Biol. Chem. [Epub: Ahead of Print] 28420728
Arias, H.R., C.M. Borghese, A.L. Germann, S.R. Pierce, A. Bonardi, A. Nocentini, P. Gratteri, T.M. Thodati, N.J. Lim, R.A. Harris, and G. Akk. (2022). (+)-Catharanthine potentiates the GABA receptor by binding to a transmembrane site at the β(+)/α(-) interface near the TM2-TM3 loop. Biochem Pharmacol 199: 114993. 35304861
Arias, H.R., S.R. Pierce, A.L. Germann, S.Q. Xu, M.O. Ortells, S. Sakamoto, D. Manetti, M.N. Romanelli, I. Hamachi, and G. Akk. (2023). Mol Pharmacol. [Epub: Ahead of Print] 37316350
Arslan, A. (2023). Pathogenic variants of human GABRA1 gene associated with epilepsy: A computational approach. Heliyon 9: e20218. 37809401
Asahi, M., K. Yamato, F. Ozoe, and Y. Ozoe. (2023). External amino acid residues of insect GABA receptor channels dictate the action of the isoxazoline ectoparasiticide fluralaner. Pest Manag Sci. [Epub: Ahead of Print] 37288963
Ashcroft, F.M. (2000). Ion Channels and Disease. San Diego: Academic Press.
Atif, M., A. Estrada-Mondragon, B. Nguyen, J.W. Lynch, and A. Keramidas. (2017). Effects of glutamate and ivermectin on single glutamate-gated chloride channels of the parasitic nematode H. contortus. PLoS Pathog 13: e1006663. 28968469
Auerbach, A. (2024). Dynamics of receptor activation by agonists. Biophys. J. [Epub: Ahead of Print] 38178577
Baenziger, J.E. and P.J. Corringer. (2011). 3D structure and allosteric modulation of the transmembrane domain of pentameric ligand-gated ion channels. Neuropharmacology 60: 116-125. 20713066
Baenziger, J.E., J.A. Domville, and J.P.D. Therien. (2017). The Role of Cholesterol in the Activation of Nicotinic Acetylcholine Receptors. Curr Top Membr 80: 95-137. 28863823
Baier, C.J., J. Fantini, and F.J. Barrantes. (2011). Disclosure of cholesterol recognition motifs in transmembrane domains of the human nicotinic acetylcholine receptor. Sci Rep 1: 69. 22355588
Baker, C., B.L. Sturt, and B.A. Bamber. (2010). Multiple roles for the first transmembrane domain of GABAA receptor subunits in neurosteroid modulation and spontaneous channel activity. Neurosci Lett 473: 242-247. 20193738
Barrantes, F.J. (2023). Structure and function meet at the nicotinic acetylcholine receptor-lipid interface. Pharmacol Res 190: 106729. 36931540
Barrantes, F.J. and J. Fantini. (2016). From hopanoids to cholesterol: Molecular clocks of pentameric ligand-gated ion channels. Prog Lipid Res 63: 1-13. 27084463
Basak, S., Y. Gicheru, S. Rao, M.S.P. Sansom, and S. Chakrapani. (2018). Cryo-EM reveals two distinct serotonin-bound conformations of full-length 5-HT receptor. Nature 563: 270-274. 30401837
Baylis, H.A., K. Matsuda, M.D. Squire, J.T. Fleming, R.J. Harvey, M.G. Darlison, E.A. Barnard, and D.B. Sattelle. (1997). ACR-3, a Caenorhabditis elegans nicotinic acetylcholine receptor subunit. Molecular cloning and functional expression. Receptors Channels 5: 149-58. 9606719
Beg, A.A. and E.M. Jorgensen. (2003). EXP-1 is an excitatory GABA-gated cation channel. Nature Neurosci. (in press). 14555952
Bentley, G.N., A.K. Jones, and A. Agnew. (2007). ShAR2beta, a divergent nicotinic acetylcholine receptor subunit from the blood fluke Schistosoma. Parasitology 134: 833-840. 17214911
Blednov, Y.A., C.M. Borghese, C.I. Ruiz, M.A. Cullins, A. Da Costa, E.A. Osterndorff-Kahanek, G.E. Homanics, and R.A. Harris. (2017). Mutation of the inhibitory ethanol site in GABA ρ1 receptors promotes tolerance to ethanol-induced motor incoordination. Neuropharmacology 123: 201-209. 28623169
Blythe, J., F.G.P. Earley, K. Piekarska-Hack, L. Firth, J. Bristow, E.A. Hirst, J.A. Goodchild, E. Hillesheim, and A.J. Crossthwaite. (2022). The mode of action of isocycloseram: A novel isoxazoline insecticide. Pestic Biochem Physiol 187: 105217. 36127059
Bocquet, N., H. Nury, M. Baaden, C. Le Poupon, J.P. Changeux, M. Delarue, and P.J. Corringer. (2009). X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature 457: 111-114. 18987633
Bocquet, N., L. Prado de Carvalho, J. Cartaud, J. Neyton, C. Le Poupon, A. Taly, T. Grutter, J.P. Changeux, and P.J. Corringer. (2007). A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family. Nature 445: 116-119. 17167423
Bondarenko V., Mowrey D., Liu LT., Xu Y. and Tang P. (2013). NMR resolved multiple anesthetic binding sites in the TM domains of the alpha4beta2 nAChR. Biochim Biophys Acta. 1828(2):398-404. 23000369
Bondarenko V., Mowrey DD., Tillman TS., Seyoum E., Xu Y. and Tang P. (2014). NMR structures of the human alpha7 nAChR transmembrane domain and associated anesthetic binding sites. Biochim Biophys Acta. 1838(5):1389-95. 24384062
Bondarenko, V., Q. Chen, K. Singewald, N. Haloi, T.S. Tillman, R.J. Howard, E. Lindahl, Y. Xu, and P. Tang. (2023). Structural Elucidation of Ivermectin Binding to α7nAChR and the Induced Channel Desensitization. ACS Chem Neurosci 14: 1156-1165. 36821490
Borghese, C.M., H.L. Wang, S.F. McHardy, R.O. Messing, J.R. Trudell, R.A. Harris, and E.J. Bertaccini. (2021). Modulation of α1β3γ2 GABA receptors expressed in oocytes using a propofol photoswitch tethered to the transmembrane helix. Proc. Natl. Acad. Sci. USA 118:. 33593898
Bouzat, C., F. Gumilar, G. Spitzmaul, H.-L. Wang, D. Rayes, S.B. Hansen, P. Taylor, and S.M. Sine. (2004). Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel. Nature 430: 896-900. 15318223
Breitinger, U., H. Sticht, and H.G. Breitinger. (2021). Modulation of recombinant human alpha 1 glycine receptor by flavonoids and gingerols. Biol Chem 402: 825-838. 33752269
Brejc, K., W.J. van Dijk, R.V. Klaassen, M. Schuurmans, J. van der Oost, A.B. Smit, and T.K. Sixma. (2001). Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 411: 269-276. 11357122
Brockmöller, S., T. Seeger, F. Worek, and S. Rothmiller. (2023). Recombinant cellular model system for human muscle-type nicotinic acetylcholine receptor α1β1δε. Cell Stress Chaperones 28: 1013-1025. 38006565
Brömstrup, T., R.J. Howard, J.R. Trudell, R.A. Harris, and E. Lindahl. (2013). Inhibition versus potentiation of ligand-gated ion channels can be altered by a single mutation that moves ligands between intra- and intersubunit sites. Structure 21: 1307-1316. 23891290
Brownlow, S., R. Webster, R. Croxen, M. Brydson, B. Neville, J.P. Lin, A. Vincent, J. Newsom-Davis, and D. Beeson. (2001). Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita. J. Clin. Invest. 108: 125-130. 11435464
Budelier, M.M., W.W.L. Cheng, Z.W. Chen, J.R. Bracamontes, Y. Sugasawa, K. Krishnan, L. Mydock-McGrane, D.F. Covey, and A.S. Evers. (2019). Common binding sites for cholesterol and neurosteroids on a pentameric ligand-gated ion channel. Biochim. Biophys. Acta. Mol. Cell Biol. Lipids 1864: 128-136. 30471426
Burzomato, V., M. Beato, P.J. Groot-Kormelink, D. Colquhoun, and L.G. Sivilotti. (2004). Single-channel behavior of heteromeric α1β glycine receptors: an attempt to detect a conformational change before the channel opens. J. Neurosci. 24: 10924-10940. 15574743
Butler, K.M., O.A. Moody, E. Schuler, J. Coryell, J.J. Alexander, A. Jenkins, and A. Escayg. (2018). De novo variants in GABRA2 and GABRA5 alter receptor function and contribute to early-onset epilepsy. Brain 141: 2392-2405. 29961870
Camacho-Hernandez, G.A. and P. Taylor. (2020). Lessons from nature: Structural studies and drug design driven by a homologous surrogate from invertebrates, AChBP. Neuropharmacology 108108. [Epub: Ahead of Print] 32353365
Cao, Y., H. Yan, G. Yu, and R. Su. (2019). Flumazenil-insensitive benzodiazepine binding sites in GABA receptors contribute to benzodiazepine-induced immobility in zebrafish larvae. Life Sci 239: 117033. 31697950
Cascio M. (2004). Structure and function of the glycine receptor and related nicotinicoid receptors. J. Biol. Chem. 279: 19383-19386. 15023997
Castro Janer, E., G.M. Klafke, F. Fontes, M.L. Capurro, and T.S.S. Schumaker. (2019). Mutations in Rhipicephalus microplus GABA gated chloride channel gene associated with fipronil resistance. Ticks Tick Borne Dis. [Epub: Ahead of Print] 30898542
Cerdan, A.H., L. Peverini, J.P. Changeux, P.J. Corringer, and M. Cecchini. (2022). Lateral fenestrations in the extracellular domain of the glycine receptor contribute to the main chloride permeation pathway. Sci Adv 8: eadc9340. 36240268
Chatzidaki A. and Millar NS. (2015). Allosteric modulation of nicotinic acetylcholine receptors. Biochem Pharmacol. 97(4):408-17. 26231943
Chen, I.S., M. Tateyama, Y. Fukata, M. Uesugi, and Y. Kubo. (2017). Ivermectin activates GIRK channels in a PIP2 -dependent, Gβγ -independent manner and an amino acid residue at the slide helix governs the activation. J. Physiol. [Epub: Ahead of Print] 28715108
Chen, Q., M.M. Wells, P. Arjunan, T.S. Tillman, A.E. Cohen, Y. Xu, and P. Tang. (2018). Structural basis of neurosteroid anesthetic action on GABA receptors. Nat Commun 9: 3972. 30266951
Chen, Q., M.M. Wells, T.S. Tillman, M.N. Kinde, A. Cohen, Y. Xu, and P. Tang. (2016). Structural Basis of Alcohol Inhibition of the Pentameric Ligand-Gated Ion Channel ELIC. Structure. [Epub: Ahead of Print] 27916519
Chen, Y., K. Reilly, and Y. Chang. (2006). Evolutionarily conserved allosteric network in the Cys loop family of ligand-gated ion channels revealed by statistical covariance analyses. J. Biol. Chem. 281: 18184-18192. 16595655
Cheng, W.W.L., Z.W. Chen, J.R. Bracamontes, M.M. Budelier, K. Krishnan, D.J. Shin, C. Wang, X. Jiang, D.F. Covey, G. Akk, and A.S. Evers. (2018). Mapping two neurosteroid-modulatory sites in the prototypic pentameric ligand-gated ion channel GLIC. J. Biol. Chem. 293: 3013-3027. 29301936
Cheng, X., I. Ivanov, H. Wang, S.M. Sine, and J.A. McCammon. (2009). Molecular-dynamics simulations of ELIC-a prokaryotic homologue of the nicotinic acetylcholine receptor. Biophys. J. 96: 4502-4513. 19486673
Chiara, D.C., S.S. Jayakar, X. Zhou, X. Zhang, P.Y. Savechenkov, K.S. Bruzik, K.W. Miller, and J.B. Cohen. (2013). Specificity of intersubunit general anesthetic-binding sites in the transmembrane domain of the human α1β3γ2 γ-aminobutyric acid type A (GABAA) receptor. J. Biol. Chem. 288: 19343-19357. 23677991
Chiara, D.C., Z. Dostalova, S.S. Jayakar, X. Zhou, K.W. Miller, and J.B. Cohen. (2012). Mapping general anesthetic binding site(s) in human α1β3 γ-aminobutyric acid type A receptors with [³H]TDBzl-etomidate, a photoreactive etomidate analogue. Biochemistry 51: 836-847. 22243422
Chiodo, L., T.E. Malliavin, L. Maragliano, G. Cottone, and G. Ciccotti. (2015). A Structural Model of the Human α7 Nicotinic Receptor in an Open Conformation. PLoS One 10: e0133011. 26208301
Chiodo, L., T.E. Malliavin, S. Giuffrida, L. Maragliano, and G. Cottone. (2018). Closed-Locked and Apo-Resting State Structures of the Human α7 Nicotinic Receptor: A Computational Study. J Chem Inf Model 58: 2278-2293. 30359518
Chisari, M., K. Wu, C.F. Zorumski, and S. Mennerick. (2011). Hydrophobic anions potently and uncompetitively antagonize GABA(A) receptor function in the absence of a conventional binding site. Br J Pharmacol 164: 667-680. 21457224
Çiçek, S.S. (2018). Structure-Dependent Activity of Natural GABA(A) Receptor Modulators. Molecules 23:. 29932138
Colon-Saez JO. and Yakel JL. (2014). A mutation in the extracellular domain of the alpha7 nAChR reduces calcium permeability. Pflugers Arch. 466(8):1571-9. 24177919
Connolly, C.N. (2008). Trafficking of 5-HT(3) and GABA(A) receptors (Review). Mol. Membr. Biol. 25: 293-301. 18446615
Corringer, P.J., M. Baaden, N. Bocquet, M. Delarue, V. Dufresne, H. Nury, M. Prevost, and C. Van Renterghem. (2010). Atomic structure and dynamics of pentameric ligand-gated ion channels: new insight from bacterial homologues. J. Physiol. 588: 565-572. 19995852
Costa, B., E. Da Pozzo, and C. Martini. (2012). Translocator protein as a promising target for novel anxiolytics. Curr Top Med Chem 12: 270-285. 22204481
Cottone, G., L. Chiodo, and L. Maragliano. (2020). Thermodynamics and Kinetics of Ion Permeation in Wild-Type and Mutated Open Active Conformation of the Human α7 Nicotinic Receptor. J Chem Inf Model. [Epub: Ahead of Print] 32803965
Crnjar, A. and C. Molteni. (2021). Cholesterol content in the membrane promotes key lipid-protein interactions in a pentameric serotonin-gated ion channel. Biointerphases 15: 061018. 33397116
Crnjar, A., F. Comitani, W. Hester, and C. Molteni. (2019). Trans- Cis Proline Switches in a Pentameric Ligand-Gated Ion Channel: How They Are Affected by and How They Affect the Biomolecular Environment. J Phys Chem Lett 10: 694-700. 30668119
Crowther, K.M., S.M. Mesoy, and S.C.R. Lummis. (2022). Residues in the 1st Transmembrane-Spanning Helix Are Important for GABA Receptor Function. Biomolecules 12:. 36139090
Culetto, E., H.A. Baylis, J.E. Richmond, A.K. Jones, J.T. Fleming, M.D. Squire, J.A. Lewis, and D.B. Sattelle. (2004). The Caenorhabditis elegans unc-63 gene encodes a levamisole-sensitive nicotinic acetylcholine receptor alpha subunit. J. Biol. Chem. 279: 42476-42483. 15280391
Cully, D.F., D.K. Vassilatis, K.K. Liu, P.S. Paress, L.H. Van der Ploeg, J.M. Schaeffer, and J.P. Arena. (1994). Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 371: 707-711. 7935817
Cymes, G.D. and C. Grosman. (2021). Signal transduction through Cys-loop receptors is mediated by the nonspecific bumping of closely apposed domains. Proc. Natl. Acad. Sci. USA 118:. 33785596
Cymes, G.D., Y. Ni, and C. Grosman. (2005). Probing ion-channel pores one proton at a time. Nature 438: 975-980. 16355215
da Costa Couto, A.R.G.M., K.L. Price, S. Mesoy, E. Capes, and S.C.R. Lummis. (2020). The M4 Helix Is Involved in α7 nACh Receptor Function. ACS Chem Neurosci. [Epub: Ahead of Print] 32364364
Dämgen, M.A. and P.C. Biggin. (2021). State-dependent protein-lipid interactions of a pentameric ligand-gated ion channel in a neuronal membrane. PLoS Comput Biol 17: e1007856. 33571182
Darwish, M., S. Hattori, H. Nishizono, T. Miyakawa, N. Yachie, and K. Takao. (2023). Comprehensive behavioral analyses of mice with a glycine receptor alpha 4 deficiency. Mol Brain 16: 44. 37217969
Das, P. and G.H. Dillon. (2005). Molecular determinants of picrotoxin inhibition of 5-hydroxytryptamine type 3 receptors. J Pharmacol Exp Ther 314: 320-328. 15814570
Das, P., C.L. Bell-Horner, R.Q. Huang, A. Raut, E.B. Gonzales, Z.L. Chen, D.F. Covey, and G.H. Dillon. (2004). Inhibition of type A GABA receptors by L-type calcium channel blockers. Neuroscience 124: 195-206. 14960351
de Almeida, R.F., L.M. Loura, M. Prieto, A. Watts, A. Fedorov, and F.J. Barrantes. (2004). Cholesterol modulates the organization of the gammaM4 transmembrane domain of the muscle nicotinic acetylcholine receptor. Biophys. J. 86: 2261-2272. 15041665
Deba, F., H.I. Ali, A. Tairu, K. Ramos, J. Ali, and A.K. Hamouda. (2018). LY2087101 and dFBr share transmembrane binding sites in the (α4)3(β2)2 Nicotinic Acetylcholine Receptor. Sci Rep 8: 1249. 29352227
Degani-Katzav, N., R. Gortler, M. Weissman, and Y. Paas. (2017). Mutational Analysis at Intersubunit Interfaces of an Anionic Glutamate Receptor Reveals a Key Interaction Important for Channel Gating by Ivermectin. Front Mol Neurosci 10: 92. 28428744
Dellisanti, C.D., B. Ghosh, S.M. Hanson, J.M. Raspanti, V.A. Grant, G.M. Diarra, A.M. Schuh, K. Satyshur, C.S. Klug, and C. Czajkowski. (2013). Site-directed spin labeling reveals pentameric ligand-gated ion channel gating motions. PLoS Biol 11: e1001714. 24260024
Dent, J.A., M.M. Smith, D.K. Vassilatis, and L. Avery. (2000). The genetics of ivermectin resistance in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 97: 2674-2679. 10716995
Di Maio, D., B. Chandramouli, and G. Brancato. (2015). Pathways and Barriers for Ion Translocation through the 5-HT3A Receptor Channel. PLoS One 10: e0140258. 26465896
Di Scala, C., C.J. Baier, L.S. Evans, P.T.F. Williamson, J. Fantini, and F.J. Barrantes. (2017). Relevance of CARC and CRAC Cholesterol-Recognition Motifs in the Nicotinic Acetylcholine Receptor and Other Membrane-Bound Receptors. Curr Top Membr 80: 3-23. 28863821
Díaz-Otero, F., M. Quesada, J. Morales-Corraliza, C. Martínez-Parra, P. Gómez-Garre, and J.M. Serratosa. (2008). Autosomal dominant nocturnal frontal lobe epilepsy with a mutation in the CHRNB2 gene. Epilepsia 49: 516-520. 17900292
Dietzen, N.M., M.J. Arcario, L.J. Chen, J.T. Petroff, 2nd, K.T. Moreland, K. Krishnan, G. Brannigan, D.F. Covey, and W.W. Cheng. (2022). Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites. Elife 11:. 34982031
Djebaili, R., S. Kenouche, I. Daoud, N. Melkemi, A. Belkadi, and F. Mesli. (2022). Investigation of [H]diazepam derivatives as allosteric modulators of GABAA receptor αβγ subtypes: combination of molecular docking/dynamic simulations, pharmacokinetics/drug-likeness prediction, and QSAR analysis. Struct Chem 1-33. [Epub: Ahead of Print] 35971551
Du J., Dong H. and Zhou HX. (2012). Size matters in activation/inhibition of ligand-gated ion channels. Trends Pharmacol Sci. 33(9):482-93. 22789930
Du J., Lu W., Wu S., Cheng Y. and Gouaux E. (2015). Glycine receptor mechanism elucidated by electron cryo-microscopy. Nature. 526(7572):224-9. 26344198
Dube, F., A. Hinas, N. Delhomme, M. Åbrink, S. Svärd, and E. Tydén. (2023). Transcriptomics of ivermectin response in Caenorhabditis elegans: Integrating abamectin quantitative trait loci and comparison to the Ivermectin-exposed DA1316 strain. PLoS One 18: e0285262. 37141255
Dworakowska, B., E. Nurowska, and K. Dołowy. (2018). Hydrocortisone inhibition of wild-type and αD200Q nicotinic acetylcholine receptors. Chem Biol Drug Des 92: 1610-1617. 29729083
El Achkar, C.M., M. Harrer, L. Smith, M. Kelly, S. Iqbal, S. Maljevic, C.E. Niturad, L.E.L.M. Vissers, A. Poduri, E. Yang, D. Lal, H. Lerche, R.S. Møller, H.E. Olson, and. (2021). Characterization of the GABRB2-Associated Neurodevelopmental Disorders. Ann Neurol 89: 573-586. 33325057
Fabiani, C., V.N. Georgiev, D.A. Peñalva, L. Sigaut, L. Pietrasanta, J. Corradi, R. Dimova, and S.S. Antollini. (2022). Membrane lipid organization and nicotinic acetylcholine receptor function: A two-way physiological relationship. Arch Biochem Biophys 730: 109413. 36183844
Fahrenbach, V.S. and E.J. Bertaccini. (2018). Insights Into Receptor-Based Anesthetic Pharmacophores and Anesthetic-Protein Interactions. Methods Enzymol 602: 77-95. 29588042
Falk-Petersen, C.B., F. Rostrup, R. Löffler, S. Buchleithner, K. Harpsøe, D.E. Gloriam, B. Frølund, and P. Wellendorph. (2021). Molecular Determinants Underlying Delta Selective Compound 2 Activity at -Containing GABA Receptors. Mol Pharmacol 100: 46-56. 33990405
Fantasia, R.J., A. Nourmahnad, E. Halpin, and S.A. Forman. (2021). Substituted Cysteine Modification and Protection with -Alkyl- Methanethiosulfonate Reagents Yields a Precise Estimate of the Distance between Etomidate and a Residue in Activated GABA Type A Receptors. Mol Pharmacol 99: 426-434. 33766924
Faulkner, C., D.F. Plant, and N.H. de Leeuw. (2019). Modulation of the Ion Channel by Fentanyl: A Molecular Dynamics Study. Biochemistry 58: 4804-4808. 31718178
Feng, H.J. and S.A. Forman. (2018). Comparison of αβδ and αβγ GABA receptors: Allosteric modulation and identification of subunit arrangement by site-selective general anesthetics. Pharmacol Res 133: 289-300. 29294355
Feng, Z., W. Li, A. Ward, B.J. Piggott, E.R. Larkspur, P.W. Sternberg, and X.Z. Xu. (2006). A C. elegans model of nicotine-dependent behavior: regulation by TRP-family channels. Cell 127: 621-633. 17081982
Filippova, N., V.E. Wotring, and D.S. Weiss. (2004). Evidence that the TM1-TM2 loop contributes to the ρ1 GABA receptor pore. J. Biol. Chem. 279: 20906-20914. 15007065
Fisher, J.L. (2004). A mutation in the GABAA receptor alpha 1 subunit linked to human epilepsy affects channel gating properties. Neuropharmacology 46: 629-637. 14996540
Fisher, J.L. (2009). The anti-convulsant stiripentol acts directly on the GABA(A) receptor as a positive allosteric modulator. Neuropharmacology 56: 190-197. 18585399
Forman, S.A. and K.W. Miller. (2016). Mapping General Anesthetic Sites in Heteromeric γ-Aminobutyric Acid Type A Receptors Reveals a Potential For Targeting Receptor Subtypes. Anesth Analg 123: 1263-1273. 27167687
Fourati, Z., R.J. Howard, S.A. Heusser, H. Hu, R.R. Ruza, L. Sauguet, E. Lindahl, and M. Delarue. (2018). Structural Basis for a Bimodal Allosteric Mechanism of General Anesthetic Modulation in Pentameric Ligand-Gated Ion Channels. Cell Rep 23: 993-1004. 29694907
Fricska, D.I., S.M. Mesoy, and S.C.R. Lummis. (2023). The MA Helix Is Important for Receptor Assembly and Function in the α4β2 nACh Receptor. Membranes (Basel) 13:. 38132895
Fritsch, S., I. Ivanov, H. Wang, and X. Cheng. (2011). Ion selectivity mechanism in a bacterial pentameric ligand-gated ion channel. Biophys. J. 100: 390-398. 21244835
Fucile, S. (2017). The Distribution of Charged Amino Acid Residues and the Ca2+ Permeability of Nicotinic Acetylcholine Receptors: A Predictive Model. Front Mol Neurosci 10: 155. 28611586
Furukawa, T. and A. Fukuda. (2023). Maternal taurine as a modulator of Cl homeostasis as well as of glycine/GABA receptors for neocortical development. Front Cell Neurosci 17: 1221441. 37601283
Furutani, S., D. Okuhara, A. Hashimoto, M. Ihara, K. Kai, H. Hayashi, D.B. Sattelle, and K. Matsuda. (2017). An L319F mutation in transmembrane region 3 (TM3) selectively reduces sensitivity to okaramine B of the Bombyx mori l-glutamate-gated chloride channel. Biosci. Biotechnol. Biochem. 1-7. [Epub: Ahead of Print] 28825521
Gallagher, C.I., D.A. Ha, R.J. Harvey, and R.J. Vandenberg. (2022). Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies. Pharmacol Rev 74: 933-961. 36779343
Garifulina, A., T. Friesacher, M. Stadler, E.M. Zangerl-Plessl, M. Ernst, A. Stary-Weinzinger, A. Willam, and S. Hering. (2022). β subunits of GABA receptors form proton-gated chloride channels: Insights into the molecular basis. Commun Biol 5: 784. 35922471
Gasiorek, A., S.M. Trattnig, P.K. Ahring, U. Kristiansen, B. Frølund, K. Frederiksen, and A.A. Jensen. (2016). Delineation of the functional properties and the mechanism of action of TMPPAA, an allosteric agonist and positive allosteric modulator of 5-HT3 receptors. Biochem Pharmacol 110-111: 92-108. 27086281
Gc, J.B., C.T. Szlenk, A. Diyaolu, P. Obi, H. Wei, X. Shi, K.M. Gibson, S. Natesan, and J.B. Roullet. (2023). Allosteric Modulation of α1β3γ2 GABA Receptors by Farnesol Through the Neurosteroid Sites. Biophys. J. [Epub: Ahead of Print] 36721367
Ge, Y., Y. Kang, R.M. Cassidy, K.M. Moon, R. Lewis, R.O.L. Wong, L.J. Foster, and A.M. Craig. (2018). Clptm1 Limits Forward Trafficking of GABA Receptors to Scale Inhibitory Synaptic Strength. Neuron. 97: 596-610.e8. 29395912
Germann, A.L., A.B. Burbridge, S.R. Pierce, and G. Akk. (2022). Activation of the Rat α1β2ε GABA Receptor by Orthosteric and Allosteric Agonists. Biomolecules 12:. 35883422
Ghosh B., Satyshur KA. and Czajkowski C. (2013). Propofol binding to the resting state of the gloeobacter violaceus ligand-gated ion channel (GLIC) induces structural changes in the inter- and intrasubunit transmembrane domain (TMD) cavities. J Biol Chem. 288(24):17420-31. 23640880
Ghosh, R., E.C. Andersen, J.A. Shapiro, J.P. Gerke, and L. Kruglyak. (2012). Natural variation in a chloride channel subunit confers avermectin resistance in C. elegans. Science 335: 574-578. 22301316
Gibbs, E., E. Klemm, D. Seiferth, A. Kumar, S.L. Ilca, P.C. Biggin, and S. Chakrapani. (2023). Conformational transitions and allosteric modulation in a heteromeric glycine receptor. Nat Commun 14: 1363. 36914669
Gielen, M., P. Thomas, and T.G. Smart. (2015). The desensitization gate of inhibitory Cys-loop receptors. Nat Commun 6: 6829. 25891813
Gill, J.K., M. Savolainen, G.T. Young, R. Zwart, E. Sher, and N.S. Millar. (2011). Agonist activation of alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site. Proc. Natl. Acad. Sci. USA 108: 5867-5872. 21436053
Gill-Thind, J.K., P. Dhankher, J.M. D'Oyley, T.D. Sheppard, and N.S. Millar. (2015). Structurally similar allosteric modulators of α7 nicotinic acetylcholine receptors exhibit five distinct pharmacological effects. J. Biol. Chem. 290: 3552-3562. 25516597
Gimenez C., Perez-Siles G., Martinez-Villarreal J., Arribas-Gonzalez E., Jimenez E., Nunez E., de Juan-Sanz J., Fernandez-Sanchez E., Garcia-Tardon N., Ibanez I., Romanelli V., Nevado J., James VM., Topf M., Chung SK., Thomas RH., Desviat LR., Aragon C., Zafra F., Rees MI., Lapunzina P., Harvey RJ. and Lopez-Corcuera B. (2012). A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2. J Biol Chem. 287(34):28986-9002. 22753417
Gisselmann, G., J. Plonka, H. Pusch, and H. Hatt. (2004). Drosophila melanogaster GRD and LCCH3 subunits form heteromultimeric GABA-gated cation channels. Br J Pharmacol 142: 409-413. 15148245
Godellas, N.E. and C. Grosman. (2022). Probing function in ligand-gated ion channels without measuring ion transport. J Gen Physiol 154:. 35612603
Gonzalez-Gutierrez G. and Grosman C. (2015). The atypical cation-conduction and gating properties of ELIC underscore the marked functional versatility of the pentameric ligand-gated ion-channel fold. J Gen Physiol. 146(1):15-36. 26078054
Gonzalez-Gutierrez, G., L.G. Cuello, S.K. Nair, and C. Grosman. (2013). Gating of the proton-gated ion channel from Gloeobacter violaceus at pH 4 as revealed by X-ray crystallography. Proc. Natl. Acad. Sci. USA 110: 18716-18721. 24167270
Goswami, U., M.M. Rahman, J. Teng, and R.E. Hibbs. (2023). Structural interplay of anesthetics and paralytics on muscle nicotinic receptors. Nat Commun 14: 3169. 37264005
Gottschalk, A., R.B. Almedom, T. Schedletzky, S.D. Anderson, J.R. Yates, 3rd, and W.R. Schafer. (2005). Identification and characterization of novel nicotinic receptor-associated proteins in Caenorhabditis elegans. EMBO. J. 24: 2566-2578. 15990870
Goyal, R., A.A. Salahudeen, and M. Jansen. (2011). Engineering a prokaryotic Cys-loop receptor with a third functional domain. J. Biol. Chem. 286: 34635-34642. 21844195
Grupe, M., M. Grunnet, J.F. Bastlund, and A.A. Jensen. (2015). Targeting α4β2 nicotinic acetylcholine receptors in central nervous system disorders: perspectives on positive allosteric modulation as a therapeutic approach. Basic Clin Pharmacol Toxicol 116: 187-200. 25441336
Grutter, T., L.P. de Carvalho, V. Dufresne, A. Taly, and J.P. Changeux. (2006). Identification of two critical residues within the Cys-loop sequence that determine fast-gating kinetics in a pentameric ligand-gated ion channel. J Mol Neurosci 30: 63-64. 17192629
Gu, S., D. Knowland, J.A. Matta, M.L. O''Carroll, W.B. Davini, M. Dhara, H.J. Kweon, and D.S. Bredt. (2020). Hair cell α9α10 nicotinic acetylcholine receptor functional expression regulated by ligand binding and deafness gene products. Proc. Natl. Acad. Sci. USA 117: 24534-24544. 32929005
Gupta, S., S. Chakraborty, R. Vij, and A. Auerbach. (2016). A mechanism for acetylcholine receptor gating based on structure, coupling, phi, and flip. J Gen Physiol. [Epub: Ahead of Print] 27932572
Guros, N.B., A. Balijepalli, and J.B. Klauda. (2019). Microsecond-timescale simulations suggest 5-HT-mediated preactivation of the 5-HT serotonin receptor. Proc. Natl. Acad. Sci. USA. [Epub: Ahead of Print] 31871207
Hahn, L., S.B. Eickhoff, K. Mueller, L. Schilbach, H. Barthel, K. Fassbender, K. Fliessbach, J. Kornhuber, J. Prudlo, M. Synofzik, J. Wiltfang, J. Diehl-Schmid, , M. Otto, J. Dukart, and M.L. Schroeter. (2024). Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems. Elife 13:. 38224473
Haller, G., M. Kapoor, J. Budde, X. Xuei, H. Edenberg, J. Nurnberger, J. Kramer, A. Brooks, J. Tischfield, L. Almasy, A. Agrawal, K. Bucholz, J. Rice, N. Saccone, L. Bierut, and A. Goate. (2014). Rare missense variants in CHRNB3 and CHRNA3 are associated with risk of alcohol and cocaine dependence. Hum Mol Genet 23: 810-819. 24057674
Hammer, H., B.M. Bader, C. Ehnert, C. Bundgaard, L. Bunch, K. Hoestgaard-Jensen, O.H. Schroeder, J.F. Bastlund, A. Gramowski-Voß, and A.A. Jensen. (2015). A Multifaceted GABAA Receptor Modulator: Functional Properties and Mechanism of Action of the Sedative-Hypnotic and Recreational Drug Methaqualone (Quaalude). Mol Pharmacol 88: 401-420. 26056160
Hanna, M.C., P.A. Davies, T.G. Hales, and E.F. Kirkness. (2000). Evidence for expression of heteromeric serotonin 5-HT(3) receptors in rodents. J. Neurochem. 75: 240-247. 10854267
Hannan, S. and T.G. Smart. (2018). Cell surface expression of homomeric GABAA receptors depends on single residues in subunit transmembrane domains. J. Biol. Chem. [Epub: Ahead of Print] 29986886
Harpole, T.J. and C. Grosman. (2019). A Crucial Role for Side-Chain Conformation in the Versatile Charge Selectivity of Cys-Loop Receptors. Biophys. J. 116: 1667-1681. 31005237
Has, A.T.C. and M. Chebib. (2018). GABAA receptors: Various stoichiometrics of subunit arrangement in α1β3 and α1β3ε receptors. Curr Pharm Des. [Epub: Ahead of Print] 29766792
Hassan, M., S. Shahzadi, H. Raza, M.A. Abbasi, H. Alashwal, N. Zaki, A.A. Moustafa, and S.Y. Seo. (2019). Computational investigation of mechanistic insights of Aβ42 interactions against extracellular domain of nAChRα7 in Alzheimer''s disease. Int J. Neurosci. 129: 666-680. 30422726
He, W., Y. Su, H.B. Peng, and P. Tong. (2020). Dynamic heterogeneity and non-Gaussian statistics for ganglioside GM1s and acetylcholine receptors on live cell membrane. Mol. Biol. Cell mbcE19080473. [Epub: Ahead of Print] 32348189
Heath, G.R. and S. Scheuring. (2019). Advances in high-speed atomic force microscopy (HS-AFM) reveal dynamics of transmembrane channels and transporters. Curr. Opin. Struct. Biol. 57: 93-102. 30878714
Henault CM., Juranka PF. and Baenziger JE. (2015). The M4 Transmembrane alpha-Helix Contributes Differently to Both the Maturation and Function of Two Prokaryotic Pentameric Ligand-gated Ion Channels. J Biol Chem. 290(41):25118-28. 26318456
Hénault, C.M. and J.E. Baenziger. (2016). Functional characterization of two prokaryotic pentameric ligand-gated ion channel chimeras - role of the GLIC transmembrane domain in proton sensing. Biochim. Biophys. Acta. [Epub: Ahead of Print] 27845033
Hénault, C.M., C. Govaerts, R. Spurny, M. Brams, A. Estrada-Mondragon, J. Lynch, D. Bertrand, E. Pardon, G.L. Evans, K. Woods, B.W. Elberson, L.G. Cuello, G. Brannigan, H. Nury, J. Steyaert, J.E. Baenziger, and C. Ulens. (2019). A lipid site shapes the agonist response of a pentameric ligand-gated ion channel. Nat Chem Biol. [Epub: Ahead of Print] 31591563
Henderson, B.J., S. Grant, B.W. Chu, R. Shahoei, S.M. Huard, S.S.M. Saladi, E. Tajkhorshid, D.A. Dougherty, and H.A. Lester. (2019). Menthol Stereoisomers Exhibit Different Effects on α4β2 nAChR Upregulation and Dopamine Neuron. Spontaneous Firing. eNeuro 5:. 30627659
Herb, A., W. Wisden, H. Lüddens, G. Puia, S. Vicini, and P.H. Seeburg. (1992). The third γ subunit of the gamma-aminobutyric acid type A receptor family. Proc. Natl. Acad. Sci. U.S.A. 89: 1433-1437. 1311098
Hernandez, C.C., W. Kong, N. Hu, Y. Zhang, W. Shen, L. Jackson, X. Liu, Y. Jiang, and R.L. Macdonald. (2017). Altered Channel Conductance States and Gating of GABAA Receptors by a Pore Mutation Linked to Dravet Syndrome. eNeuro 4:. 28197552
Hernandez, C.C., W. XiangWei, N. Hu, D. Shen, W. Shen, A.H. Lagrange, Y. Zhang, L. Dai, C. Ding, Z. Sun, J. Hu, H. Zhu, Y. Jiang, and R.L. Macdonald. (2019). Altered inhibitory synapses in de novo GABRA5 and GABRA1 mutations associated with early onset epileptic encephalopathies. Brain 142: 1938-1954. 31056671
Heusser, S.A., &.#.2.1.4.;. Yoluk, G. Klement, E.A. Riederer, E. Lindahl, and R.J. Howard. (2016). Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel. J Neurochem. [Epub: Ahead of Print] 27102368
Heusser, S.A., M. Lycksell, X. Wang, S.E. McComas, R.J. Howard, and E. Lindahl. (2018). Allosteric potentiation of a ligand-gated ion channel is mediated by access to a deep membrane-facing cavity. Proc. Natl. Acad. Sci. USA 115: 10672-10677. 30275330
Hibbs, R.E. and E. Gouaux. (2011). Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474: 54-60. 21572436
Hilf, R.J., and R. Dutzler. (2008). X-ray structure of a prokaryotic pentameric ligand-gated ion channel. Nature 452: 375-379. 18322461
Hilf, R.J., C. Bertozzi, I. Zimmermann, A. Reiter, D. Trauner, and R. Dutzler. (2010). Structural basis of open channel block in a prokaryotic pentameric ligand-gated ion channel. Nat Struct Mol Biol 17: 1330-1336. 21037567
Holden-Dye, L., M. Joyner, V. O'Connor, and R.J. Walker. (2013). Nicotinic acetylcholine receptors: a comparison of the nAChRs of Caenorhabditis elegans and parasitic nematodes. Parasitol Int 62: 606-615. 23500392
Howard, R.J. (2021). Elephants in the Dark: Insights and Incongruities in Pentameric Ligand-gated Ion Channel Models. J. Mol. Biol. 433: 167128. 34224751
Howard, R.J., S. Murail, K.E. Ondricek, P.J. Corringer, E. Lindahl, J.R. Trudell, and R.A. Harris. (2011). Structural basis for alcohol modulation of a pentameric ligand-gated ion channel. Proc. Natl. Acad. Sci. USA 108: 12149-12154. 21730162
Hu, H., &.#.1.9.3.;. Nemecz, C. Van Renterghem, Z. Fourati, L. Sauguet, P.J. Corringer, and M. Delarue. (2018). Crystal structures of a pentameric ion channel gated by alkaline pH show a widely open pore and identify a cavity for modulation. Proc. Natl. Acad. Sci. USA. [Epub: Ahead of Print] 29632192
Hu, H., K. Ataka, A. Menny, Z. Fourati, L. Sauguet, P.J. Corringer, P. Koehl, J. Heberle, and M. Delarue. (2018). Electrostatics, proton sensor, and networks governing the gating transition in GLIC, a proton-gated pentameric ion channel. Proc. Natl. Acad. Sci. USA 115: E12172-E12181. 30541892
Huang X., Chen H., Michelsen K., Schneider S. and Shaffer PL. (2015). Crystal structure of human glycine receptor-alpha3 bound to antagonist strychnine. Nature. 526(7572):277-80. 26416729
Huang Y., Wang JJ. and Yung WH. (2013). Coupling between GABA-A receptor and chloride transporter underlies ionic plasticity in cerebellar Purkinje neurons. Cerebellum. 12(3):328-30. 23341142
Huang, C., C. Xiong, and K. Kornfeld. (2004). Measurements of age-related changes of physiological processes that predict lifespan of Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 101: 8084-8089. 15141086
Huang, Q.T., C.W. Sheng, J. Jiang, T. Tang, Z.Q. Jia, Z.J. Han, and C.Q. Zhao. (2018). Interaction of insecticides with heteromeric GABA-gated chloride channels from zebrafish Danio rerio (Hamilton). J Hazard Mater 366: 643-650. [Epub: Ahead of Print] 30580138
Hussein, R.A., M. Ahmed, H. Sticht, H.G. Breitinger, and U. Breitinger. (2020). Fine-Tuning of Ion Channels-Mapping of Residues Involved in Glucose Sensitivity of Recombinant Human Glycine Receptors. ACS Chem Neurosci 11: 3474-3483. 33007159
İlhan, S.&.#.2.1.4.;., G.S.&.#.2.1.4.;. Fincan, Y. Okçay, D.S. Koç, C.&.#.3.0.4.;. Aşkın, A.K. Kibar, &.#.3.0.4.;.M. Vural, and Y. Sarıoğlu. (2022). Enhancing effect of nicotine on electrical field stimulation elicited contractile responses in isolated rabbit bladder straight muscle; the role of cannabinoid and vanilloid receptors. Turk J Med Sci 52: 1814-1820. 36945969
Ion, B.F., M.M. Wells, Q. Chen, Y. Xu, and P. Tang. (2017). Ketamine Inhibition of the Pentameric Ligand-Gated Ion Channel GLIC. Biophys. J. 113: 605-612. 28793215
Iorio, M.T., F.D. Vogel, F. Koniuszewski, P. Scholze, S. Rehman, X. Simeone, M. Schnürch, M.D. Mihovilovic, and M. Ernst. (2020). GABA Receptor Ligands Often Interact with Binding Sites in the Transmembrane Domain and in the Extracellular Domain-Can the Promiscuity Code Be Cracked? Int J Mol Sci 21:. 31947863
Iovchev, M., A. Boutanaev, I. Ivanov, A. Wolstenholme, D. Nurminsky, and E. Semenov. (2006). Phylogenetic shadowing of a histamine-gated chloride channel involved in insect vision. Insect Biochem Mol Biol 36: 10-17. 16360945
Ivanov, I., X. Cheng, S.M. Sine, and J.A. McCammon. (2007). Barriers to ion translocation in cationic and anionic receptors from the Cys-loop family. J. Am. Chem. Soc. 129: 8217-8224. 17552523
Ivica, J., R. Lape, V. Jazbec, J. Yu, H. Zhu, E. Gouaux, M.G. Gold, and L.G. Sivilotti. (2020). The intracellular domain of homomeric glycine receptors modulates agonist efficacy. J. Biol. Chem. [Epub: Ahead of Print] 32075914
Ivica, J., R. Lape, V. Jazbec, J. Yu, H. Zhu, E. Gouaux, M.G. Gold, and L.G. Sivilotti. (2021). The intracellular domain of homomeric glycine receptors modulates agonist efficacy. J. Biol. Chem. 296: 100387. [Epub: Ahead of Print] 33617876
Janzen, D., B. Slavik, M. Zehe, C. Sotriffer, H.M. Loos, A. Buettner, and C. Villmann. (2021). Sesquiterpenes and sesquiterpenoids harbor modulatory allosteric potential and affect inhibitory GABA receptor function in vitro. J Neurochem 159: 101-115. 34263932
Jayakar SS., Zhou X., Savechenkov PY., Chiara DC., Desai R., Bruzik KS., Miller KW. and Cohen JB. (2015). Positive and Negative Allosteric Modulation of an alpha1beta3gamma2 gamma-Aminobutyric Acid Type A (GABAA) Receptor by Binding to a Site in the Transmembrane Domain at the gamma+-beta- Interface. J Biol Chem. 290(38):23432-46. 26229099
Jayakar, S.S., D.C. Chiara, X. Zhou, B. Wu, K.S. Bruzik, K.W. Miller, and J.B. Cohen. (2020). Photoaffinity labeling identifies an intersubunit steroid-binding site in heteromeric GABA type A (GABA) receptors. J. Biol. Chem. 295: 11495-11512. 32540960
Jayakar, S.S., X. Zhou, D.C. Chiara, C. Jarava-Barrera, P.Y. Savechenkov, K.S. Bruzik, M. Tortosa, K.W. Miller, and J.B. Cohen. (2019). Identifying Drugs that Bind Selectively to Intersubunit General Anesthetic Sites in the 132 GABAR Transmembrane Domain. Mol Pharmacol 95: 615-628. 30952799
Jensen, M.L., A. Schousboe, and P.K. Ahring. (2005). Charge selectivity of the Cys-loop family of ligand-gated ion channels. J Neurochem 92: 217-225. 15663470
Jiang, L., Y. Li, K. Yang, Y. Wang, J. Wang, X. Cui, J. Mao, Y. Gao, P. Yi, L. Wang, and J.Y. Liu. (2020). FRMD7 Mutations Disrupt the Interaction with GABRA2 and May Result in Infantile Nystagmus Syndrome. Invest Ophthalmol Vis Sci 61: 41. 32446246
Jiao, Y., Y. Cao, Z. Zheng, M. Liu, and X. Guo. (2019). Massive expansion and diversity of nicotinic acetylcholine receptors in lophotrochozoans. BMC Genomics 20: 937. 31805848
Johannesen, K.M., S. Iqbal, M. Guazzi, N.A. Mohammadi, E. Pérez-Palma, E. Schaefer, A. De Saint Martin, M.T. Abiwarde, A. McTague, R. Pons, A. Piton, M.A. Kurian, G. Ambegaonkar, H. Firth, A. Sanchis-Juan, M. Deprez, K. Jansen, L. De Waele, E.H. Briltra, N.E. Verbeek, M. van Kempen, W. Fazeli, P. Striano, F. Zara, G. Visser, H.M.H. Braakman, M. Haeusler, M. Elbracht, U. Vaher, T. Smol, J.R. Lemke, K. Platzer, J. Kennedy, K.M. Klein, P.Y.B. Au, K. Smyth, J. Kaplan, M. Thomas, M.K. Dewenter, A. Dinopoulos, A.J. Campbell, D. Lal, D. Lederer, V.W.Y. Liao, P.K. Ahring, R.S. Møller, and E. Gardella. (2021). Structural mapping of GABRB3 variants reveals genotype-phenotype correlations. Genet Med. [Epub: Ahead of Print] 34906499
Joseph, T.T. and J.S. Mincer. (2016). Common Internal Allosteric Network Links Anesthetic Binding Sites in a Pentameric Ligand-Gated Ion Channel. PLoS One 11: e0158795. 27403526
Jospin, M., Y.B. Qi, T.M. Stawicki, T. Boulin, K.R. Schuske, H.R. Horvitz, J.L. Bessereau, E.M. Jorgensen, and Y. Jin. (2009). A neuronal acetylcholine receptor regulates the balance of muscle excitation and inhibition in Caenorhabditis elegans. PLoS Biol 7: e1000265. 20027209
Jung, S. and R.A. Harris. (2006). Sites in TM2 and 3 are critical for alcohol-induced conformational changes in GABA receptors. J Neurochem 96: 885-892. 16405501
Kaczor, P.T., A.D. Wolska, and J.W. Mozrzymas. (2021). α Subunit Histidine 55 at the Interface between Extracellular and Transmembrane Domains Affects Preactivation and Desensitization of the GABA Receptor. ACS Chem Neurosci 12: 562-572. 33471498
Kaczor, P.T., M.A. Michałowski, and J.W. Mozrzymas. (2022). α Proline 277 Residues Regulate GABAR Gating through M2-M3 Loop Interaction in the Interface Region. ACS Chem Neurosci 13: 3044-3056. 36219829
Kaiser, J., C.G.W. Gertzen, T. Bernauer, G. Höfner, K.V. Niessen, T. Seeger, F.F. Paintner, K.T. Wanner, F. Worek, H. Thiermann, and H. Gohlke. (2023). A novel binding site in the nicotinic acetylcholine receptor for MB327 can explain its allosteric modulation relevant for organophosphorus-poisoning treatment. Toxicol Lett 373: 160-171. 36503818
Kalashnyk, O., O. Lykhmus, K. Uspenska, M. Izmailov, S. Komisarenko, and M. Skok. (2020). Mitochondrial α7 nicotinic acetylcholine receptors are displaced from complexes with VDAC1 to form complexes with Bax upon apoptosis induction. Int J Biochem. Cell Biol. 129: 105879. [Epub: Ahead of Print] 33147521
Karim, N., I. Khan, A. Abdelhalim, S.A. Halim, A. Khan, and A. Al-Harrasi. (2021). Stigmasterol can be new steroidal drug for neurological disorders: Evidence of the GABAergic mechanism via receptor modulation. Phytomedicine 90: 153646. 34280827
Kelley, S.P., J.I. Dunlop, E.F. Kirkness, J.J. Lambert, and J.A. Peters. (2003). A cytoplasmic region determines single-channel conductance in 5-HT3 receptors. Nature 424: 321-324. 12867984
Keramidas A. and Lynch JW. (2013). An outline of desensitization in pentameric ligand-gated ion channel receptors. Cell Mol Life Sci. 70(7):1241-53. 22936353
Khiroug, S.S., P.C. Harkness, P.W. Lamb, S.N. Sudweeks, L. Khiroug, N.S. Millar, and J.L. Yakel. (2002). Rat nicotinic ACh receptor alpha7 and beta2 subunits co-assemble to form functional heteromeric nicotinic receptor channels. J. Physiol. 540: 425-434. 11956333
Kim, E.Y., N. Schrader, B. Smolinsky, C. Bedet, C. Vannier, G. Schwarz, and H. Schindelin. (2006). Deciphering the structural framework of glycine receptor anchoring by gephyrin. EMBO. J. 25: 1385-1395. 16511563
Kim, J.J., A. Gharpure, J. Teng, Y. Zhuang, R.J. Howard, S. Zhu, C.M. Noviello, R.M. Walsh, Jr, E. Lindahl, and R.E. Hibbs. (2020). Shared structural mechanisms of general anaesthetics and benzodiazepines. Nature 585: 303-308. 32879488
Kim, M.K., K.T. Min, and B.N. Koo. (2009). Amino acid residues involved in agonist binding and its linking to channel gating, proximal to transmembrane domain of 5-HT3A receptor for halothane modulation. Korean J Anesthesiol 56: 66-73. 30625697
Kinde, M.N., W. Bu, Q. Chen, Y. Xu, R.G. Eckenhoff, and P. Tang. (2016). Common Anesthetic-binding Site for Inhibition of Pentameric Ligand-gated Ion Channels. Anesthesiology 124: 664-673. 26756520
Klesse, G., S.J. Tucker, and M.S.P. Sansom. (2020). Electric Field Induced Wetting of a Hydrophobic Gate in a Model Nanopore Based on the 5-HT Receptor Channel. ACS Nano. [Epub: Ahead of Print] 32673478
Kodera, H., C. Ohba, M. Kato, T. Maeda, K. Araki, D. Tajima, M. Matsuo, N. Hino-Fukuyo, K. Kohashi, A. Ishiyama, S. Takeshita, H. Motoi, T. Kitamura, A. Kikuchi, Y. Tsurusaki, M. Nakashima, N. Miyake, M. Sasaki, S. Kure, K. Haginoya, H. Saitsu, and N. Matsumoto. (2016). De novo GABRA1 mutations in Ohtahara and West syndromes. Epilepsia 57: 566-573. 26918889
Kono, M., F. Ozoe, M. Asahi, and Y. Ozoe. (2022). State-dependent inhibition of GABA receptor channels by the ectoparasiticide fluralaner. Pestic Biochem Physiol 181: 105008. 35082031
Korte, M. (2019). function of Alzheimer''s protein. Science 363: 123-124. 30630916
Kudelska, M.M., L. Holden-Dye, V. O''Connor, and D.A. Doyle. (2017). Concentration-dependent effects of acute and chronic neonicotinoid exposure on the behaviour and development of the nematode Caenorhabditis elegans. Pest Manag Sci 73: 1345-1351. 28261957
Kudryashev, M., D. Castaño-Díez, C. Deluz, G. Hassaine, L. Grasso, A. Graf-Meyer, H. Vogel, and H. Stahlberg. (2016). The Structure of the Mouse Serotonin 5-HT3 Receptor in Lipid Vesicles. Structure 24: 165-170. 26724993
Kudryavtsev, D., A. Isaeva, D. Barkova, E. Spirova, R. Mukhutdinova, I. Kasheverov, and V. Tsetlin. (2021). Point Mutations of Nicotinic Receptor α1 Subunit Reveal New Molecular Features of G153S Slow-Channel Myasthenia. Molecules 26:. 33652901
Kudryavtsev, D., I. Shelukhina, C. Vulfius, T. Makarieva, V. Stonik, M. Zhmak, I. Ivanov, I. Kasheverov, Y. Utkin, and V. Tsetlin. (2015). Natural compounds interacting with nicotinic acetylcholine receptors: from low-molecular weight ones to peptides and proteins. Toxins (Basel) 7: 1683-1701. 26008231
Kumar, M., M. Kumar, J.M. Freund, and G.H. Dillon. (2017). A Single Amino Acid Residue at Transmembrane Domain 4 of the α Subunit Influences Carisoprodol Direct Gating Efficacy at GABAA Receptors. J Pharmacol Exp Ther 362: 395-404. 28642232
Kumar, P., Y. Wang, Z. Zhang, Z. Zhao, G.D. Cymes, E. Tajkhorshid, and C. Grosman. (2020). Cryo-EM structures of a lipid-sensitive pentameric ligand-gated ion channel embedded in a phosphatidylcholine-only bilayer. Proc. Natl. Acad. Sci. USA 117: 1788-1798. 31911476
Kłopotowski, K., M.A. Michałowski, M. Gos, D. Mosiądz, M.M. Czyżewska, and J.W. Mozrzymas. (2023). Mutation of valine 53 at the interface between extracellular and transmembrane domains of the β principal subunit affects the GABA receptor gating. Eur J Pharmacol 947: 175664. 36934960
Langlhofer, G. and C. Villmann. (2016). The Intracellular Loop of the Glycine Receptor: It''s not all about the Size. Front Mol Neurosci 9: 41. 27330534
Lansdell SJ., Sathyaprakash C., Doward A. and Millar NS. (2015). Activation of human 5-hydroxytryptamine type 3 receptors via an allosteric transmembrane site. Mol Pharmacol. 87(1):87-95. 25338672
Lara, C.O., C.F. Burgos, T. Silva-Grecchi, C. Muñoz-Montesino, L.G. Aguayo, J. Fuentealba, P.A. Castro, J.L. Guzmán, P.J. Corringer, G.E. Yévenes, and G. Moraga-Cid. (2019). Large Intracellular Domain-Dependent Effects of Positive Allosteric Modulators on Glycine Receptors. ACS Chem Neurosci. [Epub: Ahead of Print] 30893555
Lasala, M., J. Corradi, A. Bruzzone, M.D.C. Esandi, and C. Bouzat. (2018). A human-specific, truncated α7 nicotinic receptor subunit assembles with full-length α7 and forms functional receptors with different stoichiometries. J. Biol. Chem. [Epub: Ahead of Print] 29784875
Lee, A.G. (2021). Interfacial binding sites for cholesterol on GABA receptors and competition with neurosteroids. Biophys. J. 120: 2710-2722. 34022235
Lee, B.H., S.H. Hwang, S.H. Choi, T.J. Shin, J. Kang, S.M. Lee, and S.Y. Nah. (2011). Resveratrol enhances 5-hydroxytryptamine type 3A receptor-mediated ion currents: the role of arginine 222 residue in pre-transmembrane domain I. Biol Pharm Bull 34: 523-527. 21467640
Lefebvre, S.N., A. Taly, A. Menny, K. Medjebeur, and P.J. Corringer. (2021). Mutational analysis to explore long-range allosteric couplings involved in a pentameric channel receptor pre-activation and activation. Elife 10:. 34590583
Lev, B., S. Murail, F. Poitevin, B.A. Cromer, M. Baaden, M. Delarue, and T.W. Allen. (2017). String method solution of the gating pathways for a pentameric ligand-gated ion channel. Proc. Natl. Acad. Sci. USA 114: E4158-E4167. 28487483
Li, T., H.S. Tae, J. Liang, Z. Zhang, X. Li, T. Jiang, D.J. Adams, and R. Yu. (2024). Rational Design of Potent α-Conotoxin PeIA Analogues with Non-Natural Amino Acids for the Inhibition of Human α9α10 Nicotinic Acetylcholine Receptors. Mar Drugs 22:. 38535451
Li, Z., K.C. Chan, J.D. Nickels, and X. Cheng. (2023). Molecular Dynamics Refinement of Open State Serotonin 5-HT Receptor Structures. J Chem Inf Model 63: 1196-1207. 36757760
Lin, B., S. Xiang, and M. Li. (2016). Residues Responsible for the Selectivity of α-Conotoxins for Ac-AChBP or nAChRs. Mar Drugs 14:. 27727162
Lin, S.X.N., P.K. Ahring, A. Keramidas, V.W.Y. Liao, R.S. Møller, M. Chebib, and N.L. Absalom. (2023). Correlations of receptor desensitization of gain-of-function GABRB3 variants with clinical severity. Brain. [Epub: Ahead of Print] 37647766
Liu, H., X. Zhang, P. Shi, J. Yuan, Q. Jia, C. Pi, T. Chen, L. Xiong, J. Chen, J. Tang, R. Yue, Z. Liu, H. Shen, Y. Zuo, Y. Wei, and L. Zhao. (2023). α7 Nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect. J Neuroinflammation 20: 84. 36973813
Liu, X. and W. Wang. (2023). Asymmetric gating of a human hetero-pentameric glycine receptor. Nat Commun 14: 6377. 37821459
Liu, X. and W. Wang. (2023). Asymmetric gating of a human hetero-pentameric glycine receptor. Res Sq. 36711971
Livesey, M.R., M.A. Cooper, J.J. Lambert, and J.A. Peters. (2011). Rings of charge within the extracellular vestibule influence ion permeation of the 5-HT3A receptor. J. Biol. Chem. 286: 16008-16017. 21454663
Loser, D., K. Grillberger, M.G. Hinojosa, J. Blum, Y. Haufe, T. Danker, Y. Johansson, C. Möller, A. Nicke, S.H. Bennekou, I. Gardner, C. Bauch, P. Walker, A. Forsby, G.F. Ecker, U. Kraushaar, and M. Leist. (2021). Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling. Arch Toxicol 95: 3695-3716. 34628512
Lozon, Y., A. Sultan, S.J. Lansdell, T. Prytkova, B. Sadek, K.H. Yang, F.C. Howarth, N.S. Millar, and M. Oz. (2016). Inhibition of human α7 nicotinic acetylcholine receptors by cyclic monoterpene carveol. Eur J Pharmacol 776: 44-51. 26849939
Luger, D., G. Poli, M. Wieder, M. Stadler, S. Ke, M. Ernst, A. Hohaus, T. Linder, T. Seidel, T. Langer, S. Khom, and S. Hering. (2015). Identification of the putative binding pocket of valerenic acid on GABAA receptors using docking studies and site-directed mutagenesis. Br J Pharmacol 172: 5403-5413. 26375408
Lummis, S.C., D.L. Beene, L.W. Lee, H.A. Lester, R.W. Broadhurst, and D.A. Dougherty. (2005). Cis-trans isomerization at a proline opens the pore of a neurotransmitter-gated ion channel. Nature 438: 248-252. 16281040
Lummis, S.C.R. and D.A. Dougherty. (2022). Expression of Mutant Glycine Receptors in Oocytes Using Canonical and Non-Canonical Amino Acids Reveals Distinct Roles of Conserved Proline Residues. Membranes (Basel) 12:. 36295771
Luu, T., P.W. Gage, and M.L. Tierney. (2006). GABA increases both the conductance and mean open time of recombinant GABAA channels co-expressed with GABARAP. J. Biol. Chem. 281: 35699-35708. 16954214
Lycksell, M., U. Rovšnik, C. Bergh, N.T. Johansen, A. Martel, L. Porcar, L. Arleth, R.J. Howard, and E. Lindahl. (2021). Probing solution structure of the pentameric ligand-gated ion channel GLIC by small-angle neutron scattering. Proc. Natl. Acad. Sci. USA 118:. 34504004
Lynagh, T. and J.W. Lynch. (2012). Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin. Front Mol Neurosci 5: 60. 22586367
Lynagh, T., B.A. Cromer, V. Dufour, and B. Laube. (2014). Comparative pharmacology of flatworm and roundworm glutamate-gated chloride channels: Implications for potential anthelmintics. Int J Parasitol Drugs Drug Resist 4: 244-255. 25516835
Madjroh, N., E. Mellou, L. Æbelø, P.A. Davies, P.C. Söderhielm, and A.A. Jensen. (2021). Probing the molecular basis for signal transduction through the Zinc-Activated Channel (ZAC). Biochem Pharmacol 114781. [Epub: Ahead of Print] 34560053
Madjroh, N., E. Mellou, P.A. Davies, P.C. Söderhielm, and A.A. Jensen. (2021). Discovery and functional characterization of N-(thiazol-2-yl)-benzamide analogs as the first class of selective antagonists of the Zinc-Activated Channel (ZAC). Biochem Pharmacol 114782. [Epub: Ahead of Print] 34560054
Madjroh, N., E.R. Olander, C. Bundgaard, P.C. Söderhielm, and A.A. Jensen. (2018). Functional properties and mechanism of action of PPTQ, an allosteric agonist and low nanomolar positive allosteric modulator at GABAA receptors. Biochem Pharmacol 147: 153-169. 29155148
Maldifassi, M.C., R. Baur, and E. Sigel. (2016). Molecular mode of action of CGS 9895 at α1 β2 γ2 GABAA receptors. J Neurochem 138: 722-730. 27319298
Maldifassi, M.C., R. Baur, D. Pierce, A. Nourmahnad, S.A. Forman, and E. Sigel. (2016). Novel positive allosteric modulators of GABAA receptors with anesthetic activity. Sci Rep 6: 25943. 27198062
Manetti, D., C. Bellucci, S. Dei, E. Teodori, K. Varani, E. Spirova, D. Kudryavtsev, I. Shelukhina, V. Tsetlin, and M.N. Romanelli. (2016). New quinoline derivatives as nicotinic receptor modulators. Eur J Med Chem 110: 246-258. 26840365
Markus, F., C. Angelini, A. Trimouille, G. Rudolf, G. Lesca, C. Goizet, E. Lasseaux, B. Arveiler, M. van Slegtenhorst, A.S. Brooks, R. Abou Jamra, G.C. Korenke, J. Neidhardt, and M. Owczarek-Lipska. (2020). Rare variants in the GABA receptor subunit ε identified in patients with a wide spectrum of epileptic phenotypes. Mol Genet Genomic Med e1388. [Epub: Ahead of Print] 32588540
Martínez-Torres, A. and R. Miledi. (2013). A single amino acid change within the ion-channel domain of the γ-aminobutyric acid rho1 receptor accelerates desensitization and increases taurine agonism. Arch Med Res 35: 194-198. 15163459
Masiulis, S., R. Desai, T. Uchański, I. Serna Martin, D. Laverty, D. Karia, T. Malinauskas, J. Zivanov, E. Pardon, A. Kotecha, J. Steyaert, K.W. Miller, and A.R. Aricescu. (2019). GABA receptor signalling mechanisms revealed by structural pharmacology. Nature. [Epub: Ahead of Print] 30602790
Matsuda, K. (2021). Robust functional expression of insect nicotinic acetylcholine receptors provides new insights into neonicotinoid actions and new opportunities for pest and vector control. Pest Manag Sci 77: 3626-3630. 33202087
Mazzaferro, S., D.J. Msekela, E.C. Cooper, A. Maheshwari, and S.M. Sine. (2022). Genetic Variant in Nicotinic Receptor α4-Subunit Causes Sleep-Related Hyperkinetic Epilepsy via Increased Channel Opening. Int J Mol Sci 23:. 36292983
McCracken, M.L., C.M. Borghese, J.R. Trudell, and R.A. Harris. (2010). A transmembrane amino acid in the GABAA receptor β2 subunit critical for the actions of alcohols and anesthetics. J Pharmacol Exp Ther 335: 600-606. 20826568
McGrath, M., H. Hoyt, A. Pence, S.A. Forman, and D.E. Raines. (2021). Selective actions of benzodiazepines at the transmembrane anaesthetic binding sites of the GABA receptor: In vitro and in vivo studies. Br J Pharmacol 178: 4842-4858. 34386973
McGrath, M., H. Hoyt, A. Pence, S.S. Jayakar, X. Zhou, S.A. Forman, J.B. Cohen, K.W. Miller, and D.E. Raines. (2020). Competitive Antagonism of Etomidate Action by Diazepam. Anesthesiology 133: 583-594. 33370831
McGrath, M., M. Tolia, and D.E. Raines. (2020). The effects of a competitive antagonist on GABA-evoked currents in the presence of sedative-hypnotic agents. Pharmacol Rep 72: 260-266. 32016849
McKay, J.P., D.M. Raizen, A. Gottschalk, W.R. Schafer, and L. Avery. (2004). eat-2 and eat-18 are required for nicotinic neurotransmission in the Caenorhabditis elegans pharynx. Genetics 166: 161-169. 15020415
McKinnon, N.K., D.C. Reeves, and M.H. Akabas. (2011). 5-HT3 receptor ion size selectivity is a property of the transmembrane channel, not the cytoplasmic vestibule portals. J Gen Physiol 138: 453-466. 21948949
Menard, C., H.R. Horvitz, and S. Cannon. (2005). Chimeric mutations in the M2 segment of the 5-hydroxytryptamine-gated chloride channel MOD-1 define a minimal determinant of anion/cation permeability. J. Biol. Chem. 280: 27502-27507. 15878844
Mesoy, S., J. Jeffreys, and S.C.R. Lummis. (2019). Characterization of Residues in the 5-HT Receptor M4 Region That Contribute to Function. ACS Chem Neurosci. [Epub: Ahead of Print] 30835437
Mesoy, S.M. and S.C.R. Lummis. (2020). M4, the Outermost Helix, is Extensively Involved in Opening of the α4β2 nACh Receptor. ACS Chem Neurosci. [Epub: Ahead of Print] 33295751
Michaeli, A., I. Lerner, M. Zatsepin, S. Mezan, and A.V. Kilshtain. (2020). Discovery of novel GABAAR allosteric modulators through reinforcement learning. Curr Pharm Des. [Epub: Ahead of Print] 33185154
Milenkovic, I., A. Zimprich, M. Gencik, K. Platho-Elwischger, and S. Seidel. (2018). A novel nonsense autosomal dominant mutation in the GLRA1 gene causing hyperekplexia. J Neural Transm (Vienna) 125: 1877-1883. 30182260
Miller, D.R., H. Khoshbouei, S. Garai, L.N. Cantwell, C. Stokes, G. Thakur, and R.L. Papke. (2020). Allosterically Potentiated 7 Nicotinic Acetylcholine Receptors: Reduced Calcium Permeability and Current-Independent Control of Intracellular Calcium. Mol Pharmacol 98: 695-709. 33020143
Mineur, Y.S., A. Abizaid, Y. Rao, R. Salas, R.J. DiLeone, D. Gündisch, S. Diano, M. De Biasi, T.L. Horvath, X.B. Gao, and M.R. Picciotto. (2011). Nicotine decreases food intake through activation of POMC neurons. Science 332: 1330-1332. 21659607
Mitchell K.E., T. Iwamoto, J. Tomich, L.C. Freeman. (2000). A synthetic peptide based on a glycine-gated chloride channel induces a novel chloride conductance in isolated epithelial cells. Biochim. Biophys. Acta. 1466: 47-60. 10825430
Miyazawa, A. Y. Fujiyoshi, and N. Unwin. (2003). Structure and gating mechanism of the acetylcholine receptor pore. Nature 423: 949-955. 12827192
Mocatta, J., S.M. Mesoy, D.A. Dougherty, and S.C.R. Lummis. (2022). 5-HT Receptor MX Helix Contributes to Receptor Function. ACS Chem Neurosci 13: 2338-2345. 35867037
Moraga-Cid, G., L. Sauguet, C. Huon, L. Malherbe, C. Girard-Blanc, S. Petres, S. Murail, A. Taly, M. Baaden, M. Delarue, and P.J. Corringer. (2015). Allosteric and hyperekplexic mutant phenotypes investigated on an α1 glycine receptor transmembrane structure. Proc. Natl. Acad. Sci. USA 112: 2865-2870. 25730860
Morales-Perez, C.L., C.M. Noviello, and R.E. Hibbs. (2016). X-ray structure of the human α4β2 nicotinic receptor. Nature 538: 411-415. 27698419
Moroni, M., J.O. Meyer, C. Lahmann, and L.G. Sivilotti. (2011). In glycine and GABA(A) channels, different subunits contribute asymmetrically to channel conductance via residues in the extracellular domain. J. Biol. Chem. 286: 13414-13422. 21343294
Mukherjee, A. (2015). [Computational analysis of a cys-loop ligand gated ion channel from the green alga Chlamydomonas reinhardtii]. Mol Biol (Mosk) 49: 832-845. 26510602
Musto, E., V.W.Y. Liao, K.M. Johannesen, C.D. Fenger, D. Lederer, K. Kothur, K. Fisk, B. Bennetts, P. Vrielynck, D. Delaby, B. Ceulemans, S. Weckhuysen, P. Sparber, A. Bouman, S. Ardern-Holmes, C. Troedson, D.I. Battaglia, H. Goel, T. Feyma, S. Bakhtiari, L. Tjoa, M. Boxill, N. Demina, O. Shchagina, E. Dadali, M. Kruer, G. Cantalupo, I. Contaldo, T. Polster, B. Isidor, S.M. Bova, W. Fazeli, L. Wouters, M.J. Miranda, F. Darra, E. Pede, D. Le Duc, R.A. Jamra, S. Küry, J. Proietti, N. McSweeney, E. Brokamp, P.I. Andrews, M. Gouray Garcia, M. Chebib, R.S. Møller, P.K. Ahring, and E. Gardella. (2023). GABRA1-related disorders: from genetic to functional pathways. Ann Neurol. [Epub: Ahead of Print] 37606373
Naffaa, M.M. and A. Samad. (2016). The binding mode of picrotoxinin in GABAA-ρ receptors: Insight into the subunit''s selectivity in the transmembrane domain. Comput Biol Chem 64: 202-209. [Epub: Ahead of Print] 27423910
Nakamura, Y., M. Kondo, Y. Koyama, and S. Shimada. (2019). SR 57227A is a partial agonist/partial antagonist of 5-HT receptor and inhibits subsequent 5-HT- or SR 57227A-induced 5-HT receptor current. Biochem. Biophys. Res. Commun. 508: 590-596. 30509492
Nakao, T. and S. Banba. (2020). Important amino acids for function of the insect Rdl GABA receptor. Pest Manag Sci. [Epub: Ahead of Print] 33002317
Nakata, Y., T. Fuse, K. Yamato, M. Asahi, K. Nakahira, F. Ozoe, and Y. Ozoe. (2017). A Single Amino Acid Substitution in the Third Transmembrane Region Has Opposite Impacts on the Selectivity of the Parasiticides Fluralaner and Ivermectin for Ligand-Gated Chloride Channels. Mol Pharmacol 92: 546-555. 28887352
Nemecz, &.#.1.9.3.;., H. Hu, Z. Fourati, C. Van Renterghem, M. Delarue, and P.J. Corringer. (2017). Full mutational mapping of titratable residues helps to identify proton-sensors involved in the control of channel gating in the Gloeobacter violaceus pentameric ligand-gated ion channel. PLoS Biol 15: e2004470. [Epub: Ahead of Print] 29281623
Newcombe, J., A. Chatzidaki, T.D. Sheppard, M. Topf, and N.S. Millar. (2017). Diversity of nicotinic acetylcholine receptor positive allosteric modulators revealed by mutagenesis and a revised structural model. Mol Pharmacol. [Epub: Ahead of Print] 29196491
Nguyen, V.T., A. Ndoye, and S.A. Grando. (2000). Novel human alpha9 acetylcholine receptor regulating keratinocyte adhesion is targeted by Pemphigus vulgaris autoimmunity. Am J Pathol 157: 1377-1391. 11021840
Nielsen, B.E., I. Bermudez, and C. Bouzat. (2019). Flavonoids as positive allosteric modulators of α7 nicotinic receptors. Neuropharmacology 107794. [Epub: Ahead of Print] 31560909
Nielsen, B.E., S. Stabile, C. Vitale, and C. Bouzat. (2020). Design, Synthesis, and Functional Evaluation of a Novel Series of Phosphonate-Functionalized 1,2,3-Triazoles as Positive Allosteric Modulators of α7 Nicotinic Acetylcholine Receptors. ACS Chem Neurosci 11: 2688-2704. 32786318
Niturad, C.E., D. Lev, V.M. Kalscheuer, A. Charzewska, J. Schubert, T. Lerman-Sagie, H.Y. Kroes, R. Oegema, M. Traverso, N. Specchio, M. Lassota, J. Chelly, O. Bennett-Back, N. Carmi, T. Koffler-Brill, M. Iacomino, M. Trivisano, G. Capovilla, P. Striano, M. Nawara, S. Rzonca, U. Fischer, M. Bienek, C. Jensen, H. Hu, H. Thiele, J. Altmüller, R. Krause, P. May, F. Becker, , R. Balling, S. Biskup, S.A. Haas, P. Nürnberg, K.L.I. van Gassen, H. Lerche, F. Zara, S. Maljevic, and E. Leshinsky-Silver. (2017). Rare GABRA3 variants are associated with epileptic seizures, encephalopathy and dysmorphic features. Brain 140: 2879-2894. 29053855
Norleans, J., J. Wang, A. Kuryatov, A. Leffler, C. Doebelin, T.M. Kamenecka, and J. Lindstrom. (2019). Discovery of an intrasubunit nicotinic acetylcholine receptor binding site for the positive allosteric modulator Br-PBTC. J. Biol. Chem. [Epub: Ahead of Print] 31221718
Nury, H., C. Van Renterghem, Y. Weng, A. Tran, M. Baaden, V. Dufresne, J.P. Changeux, J.M. Sonner, M. Delarue, and P.J. Corringer. (2011). X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel. Nature 469: 428-431. 21248852
Nury, H., F. Poitevin, C. Van Renterghem, J.P. Changeux, P.J. Corringer, M. Delarue, and M. Baaden. (2010). One-microsecond molecular dynamics simulation of channel gating in a nicotinic receptor homologue. Proc. Natl. Acad. Sci. USA 107: 6275-6280. 20308576
O''Halloran, D.M. (2022). Database of glutamate-gated chloride (GluCl) subunits across 125 nematode species: patterns of gene accretion and sequence diversification. G3 (Bethesda) 12:. 35100348
Oertel, J., C. Villmann, H. Kettenmann, F. Kirchhoff, and C.M. Becker. (2007). A novel glycine receptor beta subunit splice variant predicts an unorthodox transmembrane topology. Assembly into heteromeric receptor complexes. J. Biol. Chem. 282: 2798-2807. 17145751
Oflaz, F.E., &.#.1.9.9.;.D. Son, and A. Arslan. (2019). Oligomerization and cell surface expression of recombinant GABAA receptors tagged in the δ subunit. J Integr Neurosci 18: 341-350. 31912692
Olander, E.R., D. Janzen, C. Villmann, and A.A. Jensen. (2020). Comparison of biophysical properties of α1β2 and α3β2 GABAA receptors in whole-cell patch-clamp electrophysiological recordings. PLoS One 15: e0234080. 32479525
Olander, E.R., N. Madjroh, L. Bunch, P.C. Söderhielm, and A.A. Jensen. (2018). Delineation of the functional properties and the mechanism of action of AA29504, an allosteric agonist and positive allosteric modulator of GABA receptors. Biochem Pharmacol 150: 305-319. 29454619
Oliveira, A.S.F., D.K. Shoemark, H.R. Campello, S. Wonnacott, T. Gallagher, R.B. Sessions, and A.J. Mulholland. (2019). Identification of the Initial Steps in Signal Transduction in the α4β2 Nicotinic Receptor: Insights from Equilibrium and Nonequilibrium Simulations. Structure 27: 1171-1183.e3. 31130483
Olsen, R.W. (2018). GABA receptor: Positive and negative allosteric modulators. Neuropharmacology 136: 10-22. 29407219
Pan, Z., M. Zhao, Y. Peng, and J. Wang. (2019). Functional divergence analysis of vertebrate neuronal nicotinic acetylcholine receptor subunits. J Biomol Struct Dyn 37: 2938-2948. 30044167
Pandhare, A., E. Pirayesh, A.G. Stuebler, and M. Jansen. (2019). Triple arginines as molecular determinants for pentameric assembly of the intracellular domain of 5-HT receptors. J Gen Physiol 151: 1135-1145. 31409663
Pandya, A. and J.L. Yakel. (2011). Allosteric modulator Desformylflustrabromine relieves the inhibition of α2β2 and α4β2 nicotinic acetylcholine receptors by β-amyloid(1-42) peptide. J Mol Neurosci 45: 42-47. 21424792
Pandya, A. and J.L. Yakel. (2011). Allosteric modulators of the α4β2 subtype of neuronal nicotinic acetylcholine receptors. Biochem Pharmacol 82: 952-958. 21596025
Panicker, S., H. Cruz, C. Arrabit, K.F. Suen, and P.A. Slesinger. (2004). Minimal structural rearrangement of the cytoplasmic pore during activation of the 5-HT3A receptor. J. Biol. Chem. 279: 28149-28158. 15131114
Pantazis, A., A. Segaran, C.H. Liu, A. Nikolaev, J. Rister, A.S. Thum, T. Roeder, E. Semenov, M. Juusola, and R.C. Hardie. (2008). Distinct roles for two histamine receptors (HclA and HclB) at the Drosophila photoreceptor synapse. J. Neurosci. 28: 7250-7259. 18632929
Papke, R.L., J.D. Buhr, M.M. Francis, K.I. Choi, J.S. Thinschmidt, and N.A. Horenstein. (2005). The effects of subunit composition on the inhibition of nicotinic receptors by the amphipathic blocker 2,2,6,6-tetramethylpiperidin-4-yl heptanoate. Mol Pharmacol 67: 1977-1990. 15761116
Parikh, R.B., M. Bali, and M.H. Akabas. (2011). Structure of the M2 transmembrane segment of GLIC, a prokaryotic Cys loop receptor homologue from Gloeobacter violaceus, probed by substituted cysteine accessibility. J. Biol. Chem. 286: 14098-14109. 21362624
Perić, M., I. Bečeheli, L. Čičin-Šain, G. Desoye, and J. Štefulj. (2022). Serotonin system in the human placenta - the knowns and unknowns. Front Endocrinol (Lausanne) 13: 1061317. 36531448
Peters, J.A., M.A. Cooper, J.E. Carland, M.R. Livesey, T.G. Hales, and J.J. Lambert. (2010). Novel structural determinants of single channel conductance and ion selectivity in 5-hydroxytryptamine type 3 and nicotinic acetylcholine receptors. J. Physiol. 588: 587-596. 19933751
Pfaff, J., H. Reinwald, S.U. Ayobahan, J. Alvincz, B. Göckener, O. Shomroni, G. Salinas, R.A. Düring, C. Schäfers, and S. Eilebrecht. (2021). Toxicogenomic differentiation of functional responses to fipronil and imidacloprid in Daphnia magna. Aquat Toxicol 238: 105927. [Epub: Ahead of Print] 34340001
Pierce, S.R., A.L. Germann, S.Q. Xu, S.L. Menon, M.O. Ortells, H.R. Arias, and G. Akk. (2023). Mutational Analysis of Anesthetic Binding Sites and Their Effects on GABA Receptor Activation and Modulation by Positive Allosteric Modulators of the α7 Nicotinic Receptor. Biomolecules 13:. 37189445
Pirayesh, E., A.G. Stuebler, A. Pandhare, and M. Jansen. (2019). Delineating the Site of Interaction of the 5-HT Receptor with the Chaperone Protein RIC-3. Biophys. J. [Epub: Ahead of Print] 31870537
Pirayesh, E., H.Q. Do, G. Ferreira, A. Pandhare, Z.R. Gallardo, and M. Jansen. (2023). Identification of a binding site for bupropion in ligand-gated ion channel. bioRxiv. 37873398
Price, K.L. and S.C.R. Lummis. (2018). Characterization of a 5-HT-ELIC Chimera Revealing the Sites of Action of Modulators. ACS Chem Neurosci. [Epub: Ahead of Print] 29508995
Price, K.L., Y. Hirayama, and S.C. Lummis. (2017). Subtle Differences among 5-HT3AC, 5-HT3AD, and 5-HT3AE Receptors Are Revealed by Partial Agonists. ACS Chem Neurosci. [Epub: Ahead of Print] 28367632
Puig, M.V. and A.T. Gulledge. (2011). Serotonin and prefrontal cortex function: neurons, networks, and circuits. Mol Neurobiol 44: 449-464. 22076606
Puinean AM., Lansdell SJ., Collins T., Bielza P. and Millar NS. (2013). A nicotinic acetylcholine receptor transmembrane point mutation (G275E) associated with resistance to spinosad in Frankliniella occidentalis. J Neurochem. 124(5):590-601. 23016960
Purohit, P. and A. Auerbach. (2007). Acetylcholine receptor gating: movement in the α-subunit extracellular domain. J. Gen. Physiol. 130(6):569-579. 18040059
Purohit, P., A. Mitra, and A. Auerbach. (2007). A stepwise mechanism for acetylcholine receptor channel gating. Nature 446: 930-933. 17443187
Quadri, M., S. Garai, G.A. Thakur, C. Stokes, A. Gulsevin, N.A. Horenstein, and R.L. Papke. (2018). Macroscopic and microscopic activation of α7 nicotinic acetylcholine receptors by the structurally unrelated ago-PAMs B-973B and GAT107. Mol Pharmacol. [Epub: Ahead of Print] 30348894
Raisch, T. and S. Raunser. (2023). The modes of action of ion-channel-targeting neurotoxic insecticides: lessons from structural biology. Nat Struct Mol Biol 30: 1411-1427. 37845413
Ranganathan, R., S.C. Cannon and H.R. Horvitz. (2000). MOD-1 is a serotonin-gated chloride channel that modulates locomotory behavior in C. elegans. Nature 408: 470-473. 11100728
Reeves, D.C. and S.C.R. Lummis. (2002). The molecular basis of the structure and function of the 5-HT3 receptor: a model ligand-gated ion channel. Mol. Membrane Biol. 19: 11-26. 11989819
Rice, H.C., D. de Malmazet, A. Schreurs, S. Frere, I. Van Molle, A.N. Volkov, E. Creemers, I. Vertkin, J. Nys, F.M. Ranaivoson, D. Comoletti, J.N. Savas, H. Remaut, D. Balschun, K.D. Wierda, I. Slutsky, K. Farrow, B. De Strooper, and J. de Wit. (2019). Secreted amyloid-β precursor protein functions as a GABAR1a ligand to modulate synaptic transmission. Science 363:. 30630900
Rienzo, M., S.C. Lummis, and D.A. Dougherty. (2014). Structural requirements in the transmembrane domain of GLIC revealed by incorporation of noncanonical histidine analogs. Chem Biol 21: 1700-1706. 25525989
Ringstad, N., N. Abe, and H.R. Horvitz. (2009). Ligand-gated chloride channels are receptors for biogenic amines in C. elegans. Science 325: 96-100. 19574391
Roberts, M.T., R. Phelan, B.S. Erlichman, R.N. Pillai, L. Ma, G.F. Lopreato, and S.J. Mihic. (2006). Occupancy of a single anesthetic binding pocket is sufficient to enhance glycine receptor function. J. Biol. Chem. 281: 3305-3311. 16361257
Rossokhin, A. (2020). The general anesthetic etomidate and fenamate mefenamic acid oppositely affect GABAR and GlyR: a structural explanation. Eur Biophys. J. 49: 591-607. 32940715
Rossokhin, A.V., I.N. Sharonova, A. Dvorzhak, J.V. Bukanova, and V.G. Skrebitsky. (2019). The mechanisms of potentiation and inhibition of GABA receptors by non-steroidal anti-inflammatory drugs, niflumic and mefenamic acids. Neuropharmacology 107795. [Epub: Ahead of Print] 31560908
Rovšnik, U., Y. Zhuang, B.O. Forsberg, M. Carroni, L. Yvonnesdotter, R.J. Howard, and E. Lindahl. (2021). Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulations. Life Sci Alliance 4:. 34210687
Safratowich, B.D., C. Lor, L. Bianchi, and L. Carvelli. (2013). Amphetamine activates an amine-gated chloride channel to generate behavioral effects in Caenorhabditis elegans. J. Biol. Chem. 288: 21630-21637. 23775081
Sanchis-Juan, A., M.A. Hasenahuer, J.A. Baker, A. McTague, K. Barwick, M.A. Kurian, S.T. Duarte, , K.J. Carss, J. Thornton, and F.L. Raymond. (2020). Structural analysis of pathogenic missense mutations in GABRA2 and identification of a novel de novo variant in the desensitization gate. Mol Genet Genomic Med e1106. [Epub: Ahead of Print] 32347641
Sanders, V.R. and N.S. Millar. (2023). Potentiation and allosteric agonist activation of α7 nicotinic acetylcholine receptors: binding sites and hypotheses. Pharmacol Res 191: 106759. 37023990
Sanders, V.R., A. Sweeney, M. Topf, and N.S. Millar. (2022). Stoichiometry-Selective Antagonism of α4β2 Nicotinic Acetylcholine Receptors by Fluoroquinolone Antibiotics. ACS Chem Neurosci 13: 1805-1817. 35657695
Sarang, S.S., S.M. Lukyanova, D.D. Brown, B.S. Cummings, S.R. Gullans, and R.G. Schnellmann. (2008). Identification, coassembly, and activity of γ- aminobutyric acid receptor subunits in renal proximal tubular cells. J. Pharmacol. Exp. Ther. 324: 376-382. 17959749
Sauguet L., Shahsavar A., Poitevin F., Huon C., Menny A., Nemecz A., Haouz A., Changeux JP., Corringer PJ. and Delarue M. (2014). Crystal structures of a pentameric ligand-gated ion channel provide a mechanism for activation. Proc Natl Acad Sci U S A. 111(3):966-71. 24367074
Sauguet, L., R.J. Howard, L. Malherbe, U.S. Lee, P.J. Corringer, R. Adron Harris, and M. Delarue. (2013). Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel. Nat Commun 4: 1697. 23591864
Schaefer, N., A. Berger, J. van Brederode, F. Zheng, Y. Zhang, S. Leacock, L. Littau, S. Jablonka, S. Malhotra, M. Topf, F. Winter, D. Davydova, J.W. Lynch, C.J. Paige, C. Alzheimer, R.J. Harvey, and C. Villmann. (2017). Disruption of a Structurally Important Extracellular Element in the Glycine Receptor Leads to Decreased Synaptic Integration and Signaling Resulting in Severe Startle Disease. J. Neurosci. 37: 7948-7961. 28724750
Schaefer, N., V. Roemer, D. Janzen, and C. Villmann. (2018). Impaired Glycine Receptor Trafficking in Neurological Diseases. Front Mol Neurosci 11: 291. 30186111
Schmandt, N., P. Velisetty, S.V. Chalamalasetti, R.A. Stein, R. Bonner, L. Talley, M.D. Parker, H.S. Mchaourab, V.C. Yee, D.T. Lodowski, and S. Chakrapani. (2015). A chimeric prokaryotic pentameric ligand-gated channel reveals distinct pathways of activation. J Gen Physiol 146: 323-340. 26415570
Schmauder, R., T. Eick, E. Schulz, G. Sammler, E. Voigt, G. Mayer, H. Ginter, G. Ditze, and K. Benndorf. (2023). Fast functional mapping of ligand-gated ion channels. Commun Biol 6: 1003. 37783870
Schofield, C.M. and N.L. Harrison. (2005). Transmembrane residues define the action of isoflurane at the GABAA receptor α-3 subunit. Brain Res 1032: 30-35. 15680938
Seljeset, S., D.P. Bright, P. Thomas, and T.G. Smart. (2018). Probing GABAreceptors with inhibitory neurosteroids. Neuropharmacology. [Epub: Ahead of Print] 29447845
Sgard, F., E. Charpantier, S. Bertrand, N. Walker, D. Caput, D. Graham, D. Bertrand, and F. Besnard. (2002). A novel human nicotinic receptor subunit, alpha10, that confers functionality to the alpha9-subunit. Mol Pharmacol 61: 150-159. 11752216
Shalabi, A.R., Z. Yu, X. Zhou, Y. Jounaidi, H. Chen, J. Dai, D.E. Kent, H.J. Feng, S.A. Forman, J.B. Cohen, K.S. Bruzik, and K.W. Miller. (2020). A potent photoreactive general anesthetic with novel binding site selectivity for GABA receptors. Eur J Med Chem 194: 112261. 32247113
Shan, T., C. Chen, Q. Ding, X. Chen, H. Zhang, A. Chen, X. Shi, and X. Gao. (2020). Molecular characterization and expression profiles of nicotinic acetylcholine receptors in Bradysia odoriphaga. Pestic Biochem Physiol 165: 104563. 32359542
Shen, X.M., M. Milone, H.L. Wang, B. Banwell, D. Selcen, S.M. Sine, and A.G. Engel. (2019). Slow-channel myasthenia due to novel mutation in M2 domain of AChR delta subunit. Ann Clin Transl Neurol 6: 2066-2078. 31560172
Shen, X.M., T. Okuno, M. Milone, K. Otsuka, K. Takahashi, H. Komaki, E. Giles, K. Ohno, and A.G. Engel. (2016). Mutations Causing Slow-Channel Myasthenia Reveal that a Valine ring in the Channel Pore of Muscle AChR is Optimized for Stabilizing Channel Gating. Hum Mutat. [Epub: Ahead of Print] 27375219
Shen, Y., Q. Huang, M. Ji, C.Y. Hsueh, and L. Zhou. (2022). Smoking-mediated nicotinic acetylcholine receptors (nAChRs) for predicting outcomes for head and neck squamous cell carcinomas. BMC Cancer 22: 1093. 36284268
Sheng, C.W., Z.Q. Jia, Y. Ozoe, Q.T. Huang, Z.J. Han, and C.Q. Zhao. (2018). Molecular cloning, spatiotemporal and functional expression of GABA receptor subunits RDL1 and RDL2 of the rice stem borer Chilo suppressalis. Insect Biochem Mol Biol 94: 18-27. [Epub: Ahead of Print] 29408355
Shi, S., S.N. Lefebvre, L. Peverini, A.H. Cerdan, P. Milán Rodríguez, M. Gielen, J.P. Changeux, M. Cecchini, and P.J. Corringer. (2023). Illumination of a progressive allosteric mechanism mediating the glycine receptor activation. Nat Commun 14: 795. 36781912
Shin, D.J., A.L. Germann, A.D. Johnson, S.A. Forman, J.H. Steinbach, and G. Akk. (2018). Propofol Is an Allosteric Agonist with Multiple Binding Sites on Concatemeric Ternary GABA Receptors. Mol Pharmacol 93: 178-189. 29192122
Shivers, B.D., I. Killisch, R. Sprengel, H. Sontheimer, M. Köhler, P.R. Schofield, and P.H. Seeburg. (1989). Two novel GABAA receptor subunits exist in distinct neuronal subpopulations. Neuron. 3: 327-337. 2561970
Sigel, E., R. Baur, I. Rácz, J. Marazzi, T.G. Smart, A. Zimmer, and J. Gertsch. (2011). The major central endocannabinoid directly acts at GABA(A) receptors. Proc. Natl. Acad. Sci. USA 108: 18150-18155. 22025726
Sine, S.M. and A.G. Engel. (2006). Recent advances in Cys-loop receptor structure and function. Nature 440: 448-455. 16554804
Sivilotti, L.G. (2010). What single-channel analysis tells us of the activation mechanism of ligand-gated channels: the case of the glycine receptor. J. Physiol. 588: 45-58. 19770192
Smelt, C.L.C., V.R. Sanders, J. Newcombe, R.P. Burt, T.D. Sheppard, M. Topf, and N.S. Millar. (2018). Identification by virtual screening and functional characterisation of novel positive and negative allosteric modulators of the α7 nicotinic acetylcholine receptor. Neuropharmacology 139: 194-204. 30009834
Smit, A.B., N.I. Syed, D. Schaap, J. van Minnen, J. Klumperman, K.S. Kits, H. Lodder, R.C. van der Schors, R. van Elk, B. Sorgedrager, K. Brejc, T.K. Sixma, and W.P. Geraerts. (2001). A glia-derived acetylcholine-binding protein that modulates synaptic transmission. Nature 411: 261-268. 11357121
Snell, H.D. and E.B. Gonzales. (2016). 5-(N, N-Hexamethylene) amiloride is a GABA-A ρ1 receptor positive allosteric modulator. Channels (Austin) 1-9. [Epub: Ahead of Print] 27367557
Solt, K., J.S. Johansson, and D.E. Raines. (2006). Kinetics of anesthetic-induced conformational transitions in a four-α-helix bundle protein. Biochemistry 45: 1435-1441. 16445285
Spurny R., Billen B., Howard RJ., Brams M., Debaveye S., Price KL., Weston DA., Strelkov SV., Tytgat J., Bertrand S., Bertrand D., Lummis SC. and Ulens C. (2013). Multisite binding of a general anesthetic to the prokaryotic pentameric Erwinia chrysanthemi ligand-gated ion channel (ELIC). J Biol Chem. 288(12):8355-64. 23364792
Squire, M.D., C. Tornøe, H.A. Baylis, J.T. Fleming, E.A. Barnard, and D.B. Sattelle. (1995). Molecular cloning and functional co-expression of a Caenorhabditis elegans nicotinic acetylcholine receptor subunit (acr-2). Receptors Channels 3: 107-115. 8581398
Sridhar, A., S.C.R. Lummis, D. Pasini, A. Mehregan, M. Brams, K. Kambara, D. Bertrand, E. Lindahl, R.J. Howard, and C. Ulens. (2021). Regulation of a pentameric ligand-gated ion channel by a semiconserved cationic lipid-binding site. J. Biol. Chem. 297: 100899. [Epub: Ahead of Print] 34157288
Steudle, F., S. Rehman, K. Bampali, X. Simeone, Z. Rona, E. Hauser, W.M. Schmidt, P. Scholze, and M. Ernst. (2020). A novel de novo variant of GABRA1 causes increased sensitivity for GABA in vitro. Sci Rep 10: 2379. 32047208
Stevanovic, S., D.S. Marjanović, S.M. Trailović, N. Zdravković, A. Perdih, and K. Nikolic. (2021). Potential modulating effect of the Ascaris suum nicotinic acetylcholine receptor (nAChR) by compounds GSK575594A, diazepam and flumazenil discovered by structure-based virtual screening approach. Mol Biochem Parasitol 242: 111350. 33422580
Stewart, D.S., D.W. Pierce, M. Hotta, A.T. Stern, and S.A. Forman. (2014). Mutations at beta N265 in γ-aminobutyric acid type A receptors alter both binding affinity and efficacy of potent anesthetics. PLoS One 9: e111470. 25347186
Stuebler, A.G. and M. Jansen. (2020). Mobility of Lower MA-Helices for Ion Conduction through Lateral Portals in 5-HT Receptors. Biophys. J. [Epub: Ahead of Print] 33157122
Sugasawa, Y., J.R. Bracamontes, K. Krishnan, D.F. Covey, D.E. Reichert, G. Akk, Q. Chen, P. Tang, A.S. Evers, and W.W.L. Cheng. (2019). The molecular determinants of neurosteroid binding in the GABA(A) receptor. J Steroid Biochem Mol Biol 192: 105383. [Epub: Ahead of Print] 31150831
Sumner, R.L., R.L. McMillan, A. Forsyth, S.D. Muthukumaraswamy, and A.D. Shaw. (2024). Neurophysiological evidence that frontoparietal connectivity and GABA-A receptor changes underpin the antidepressant response to ketamine. Transl Psychiatry 14: 116. 38402231
Sun, C., H. Zhu, S. Clark, and E. Gouaux. (2023). Cryo-EM structures reveal native GABA receptor assemblies and pharmacology. Nature 622: 195-201. 37730991
Sun, C., H. Zhu, S. Clark, and E. Gouaux. (2023). Regulated assembly and neurosteroid modulation constrain GABA receptor pharmacology. bioRxiv. 36824901
Sun, J., J.F. Comeau, and J.E. Baenziger. (2016). Probing the structure of the uncoupled nicotinic acetylcholine receptor. Biochim. Biophys. Acta. 1859: 146-154. [Epub: Ahead of Print] 27871840
Sundararajan, T., A.M. Manzardo, and M.G. Butler. (2018). Functional analysis of schizophrenia genes using GeneAnalytics program and integrated databases. Gene 641: 25-34. 29032150
Syding, L.A., A. Kubik-Zahorodna, D.P. Reguera, P. Nickl, B. Hruskova, M. Kralikova, J. Kopkanova, V. Novosadova, P. Kasparek, J. Prochazka, J. Rozman, R. Turecek, and R. Sedlacek. (2023). Ablation of Influences Corticosterone Levels and Anxiety-like Behavior in Mice. Genes (Basel) 14:. 36833213
Szabo, A., A. Nourmahnad, E. Halpin, and S.A. Forman. (2019). Monod-Wyman-Changeux Allosteric Shift Analysis in Mutant α1β3γ2L GABAA Receptors Indicates Selectivity and Cross-Talk Among Intersubunit Transmembrane Anesthetic Sites. Mol Pharmacol. [Epub: Ahead of Print] 30696720
Szarecka, A., Y. Xu, and P. Tang. (2007). Dynamics of heteropentameric nicotinic acetylcholine receptor: implications of the gating mechanism. Proteins 68: 948-960. 17546671
Tae, H.S., M.O. Ortells, B.J. Tekarli, D. Manetti, M.N. Romanelli, J.M. McIntosh, D.J. Adams, and H.R. Arias. (2023). DM506 (3-Methyl-1,2,3,4,5,6-hexahydroazepino[4,5-]indole fumarate), a Novel Derivative of Ibogamine, Inhibits α7 and α9α10 Nicotinic Acetylcholine Receptors by Different Allosteric Mechanisms. ACS Chem Neurosci. [Epub: Ahead of Print] 37386821
Tang, B. and S.C.R. Lummis. (2018). The roles of aromatic residues in the glycine receptor transmembrane domain. BMC Neurosci 19: 53. 30189850
Tapia, L., A. Kuryatov, and J. Lindstrom. (2007). Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry greatly exceeds that of (alpha4)2(beta2)3 human acetylcholine receptors. Mol Pharmacol 71: 769-776. 17132685
Targowska-Duda, K.M., A.A. Kaczor, K. Jozwiak, and H.R. Arias. (2019). Molecular interactions of type I and type II positive allosteric modulators with the human α7 nicotinic acetylcholine receptor: an in silico study. J Biomol Struct Dyn 37: 411-439. 29363414
Tasneem, A., L.M. Iyer, E. Jakobsson, and L. Aravind. (2005). Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels. Genome Biol 6: R4. 15642096
Terejko, K., M.A. Michałowski, I. Iżykowska, A. Dominik, A. Brzóstowicz, and J.W. Mozrzymas. (2021). Mutations at the M2 and M3 Transmembrane Helices of the GABARs α and β Subunits Affect Primarily Late Gating Transitions Including Opening/Closing and Desensitization. ACS Chem Neurosci 12: 2421-2436. 34101432
Therien, J.P. and J.E. Baenziger. (2017). Pentameric ligand-gated ion channels exhibit distinct transmembrane domain archetypes for folding/expression and function. Sci Rep 7: 450. 28348412
Thompson, A.J., H.A. Lester, and S.C. Lummis. (2010). The structural basis of function in Cys-loop receptors. Q. Rev. Biophys. 43: 449-499. 20849671
Thompson, J.R.E., C.A. Beaudoin, and S.C.R. Lummis. (2023). Modelling and Molecular Dynamics Predict the Structure and Interactions of the Glycine Receptor Intracellular Domain. Biomolecules 13:. 38136628
Thompson, M.J., J.A. Domville, and J.E. Baenziger. (2020). The functional role of the αM4 transmembrane helix in the muscle nicotinic acetylcholine receptor probed through mutagenesis and co-evolutionary analyses. J. Biol. Chem. [Epub: Ahead of Print] 32527728
Tomita, S. (2019). Molecular constituents and localization of the ionotropic GABA receptor complex in vivo. Curr Opin Neurobiol 57: 81-86. [Epub: Ahead of Print] 30784980
Tong, A., J.T. Petroff, 2nd, F.F. Hsu, P.A. Schmidpeter, C.M. Nimigean, L. Sharp, G. Brannigan, and W.W. Cheng. (2019). Direct binding of phosphatidylglycerol at specific sites modulates desensitization of a ligand-gated ion channel. Elife 8:. 31724949
Touroutine, D., R.M. Fox, S.E. Von Stetina, A. Burdina, D.M. Miller, 3rd, and J.E. Richmond. (2005). acr-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the Caenorhabditis elegans neuromuscular junction. J. Biol. Chem. 280: 27013-27021. 15917232
Towers, P.R., L. Pym, M. Yokota, K. Matsuda, and D.B. Sattelle. (2006). Alpha7 mutants mimicking atypical motifs (YxxCC of loop-C, and E to H at -1'' in TM2) in the C. elegans LEV-8 subunit affect nicotinic acetylcholine receptor function. Invert Neurosci 6: 69-73. 16758254
Trattnig, S.M., A. Gasiorek, T.Z. Deeb, E.J. Ortiz, S.J. Moss, A.A. Jensen, and P.A. Davies. (2016). Copper and protons directly activate the zinc-activated channel. Biochem Pharmacol 103: 109-117. 26872532
Treinin, M. (2008). RIC-3 and nicotinic acetylcholine receptors: biogenesis, properties, and diversity. Biotechnol J 3: 1539-1547. 18956371
Treinin, M., B. Gillo, L. Liebman, and M. Chalfie. (1998). Two functionally dependent acetylcholine subunits are encoded in a single Caenorhabditis elegans operon. Proc. Natl. Acad. Sci. USA 95: 15492-15495. 9860996
Tribiños, F., P. Cuevas, I. Cornejo, F.V. Sepúlveda, and L.P. Cid. (2023). A new family of glutamate-gated chloride channels in parasitic sea louse Caligus rogercresseyi: A subunit refractory to activation by ivermectin is dominant in heteromeric assemblies. PLoS Pathog 19: e1011188. 36917600
Tricoire-Leignel, H. and S.H. Thany. (2010). Identification of critical elements determining toxins and insecticide affinity, ligand binding domains and channel properties. Adv Exp Med Biol 683: 45-52. 20737787
Tsetlin, V., D. Kuzmin, and I. Kasheverov. (2011). Assembly of nicotinic and other Cys-loop receptors. J Neurochem 116: 734-741. 21214570
Unwin, N. (1995). Acetylcholine receptor channel imaged in the open state. Nature 373: 37-43. 7800037
Unwin, N. (2013). Nicotinic acetylcholine receptor and the structural basis of neuromuscular transmission: insights from Torpedo postsynaptic membranes. Q. Rev. Biophys. 46: 283-322. 24050525
Unwin, N. (2017). Segregation of lipids near acetylcholine-receptor channels imaged by cryo-EM. IUCrJ 4: 393-399. 28875026
Unwin, N. (2021). Protein-Lipid Interplay at the Neuromuscular Junction. Microscopy (Oxf). [Epub: Ahead of Print] 34226930
Velisetty P., Chalamalasetti SV. and Chakrapani S. (2012). Conformational transitions underlying pore opening and desensitization in membrane-embedded Gloeobacter violaceus ligand-gated ion channel (GLIC). J Biol Chem. 287(44):36864-72. 22977232
Velisetty, P., S.V. Chalamalasetti, and S. Chakrapani. (2014). Structural basis for allosteric coupling at the membrane-protein interface in Gloeobacter violaceus ligand-gated ion channel (GLIC). J. Biol. Chem. 289: 3013-3025. 24338475
Viscarra, F., J.F. Chrestia, Y. Sanchez, E.G. Pérez, P.C. Biggin, C. Bouzat, I. Bermudez, and J.J. López. (2023). Side Groups Convert the α7 Nicotinic Receptor Agonist Ether Quinuclidine into a Type I Positive Allosteric Modulator. ACS Chem Neurosci 14: 2876-2887. 37535446
Volkova, Y.A., I.V. Rassokhina, E.A. Kondrakhin, A.V. Rossokhin, S.N. Kolbaev, T.B. Tihonova, M. Kh Dzhafarov, M.A. Schetinina, E.I. Chernoburova, E.V. Vasileva, A.S. Dmitrenok, G.I. Kovalev, I.N. Sharonova, and I.V. Zavarzin. (2022). Synthesis and evaluation of avermectin-imidazo[1,2-a]pyridine hybrids as potent GABA receptor modulators. Bioorg Chem 127: 105904. 35716646
Vulfius, C.A., D.S. Lebedev, E.V. Kryukova, D.S. Kudryavtsev, S.N. Kolbaev, Y.N. Utkin, and V.I. Tsetlin. (2020). PNU-120596, a positive allosteric modulator of mammalian α7 nicotinic acetylcholine receptor, is a negative modulator of ligand-gated chloride-selective channels of the gastropod Lymnaea stagnalis. J Neurochem 155: 274-284. 32248535
Wan, L., L. Chen, J. Yu, G. Wang, Z. Wu, B. Qian, X. Liu, and Y. Wang. (2020). Coordinated downregulation of KCC2 and GABA receptor contributes to inhibitory dysfunction during seizure induction. Biochem. Biophys. Res. Commun. 532: 489-495. 32892950
Wang HL., Cheng X. and Sine SM. (2012). Intramembrane proton binding site linked to activation of bacterial pentameric ion channel. J Biol Chem. 287(9):6482-9. 22084238
Wang, H.T., C.L. Tsai, and M.E. Chen. (2018). Nicotinic acetylcholine receptor subunit α6 associated with spinosad resistance in Rhyzopertha dominica (Coleoptera: Bostrichidae). Pestic Biochem Physiol 148: 68-73. 29891379
Wang, J., X. Wang, S.J. Lansdell, J. Zhang, N.S. Millar, and Y. Wu. (2016). A three amino acid deletion in the transmembrane domain of the nicotinic acetylcholine receptor α6 subunit confers high-level resistance to spinosad in Plutella xylostella. Insect Biochem Mol Biol 71: 29-36. 26855198
Wang, N., J. Lian, Y. Cao, A. Muheyati, S. Yuan, Y. Ma, S. Zhang, G. Yu, and R. Su. (2021). High-Dose Benzodiazepines Positively Modulate GABA Receptors via a Flumazenil-Insensitive Mechanism. Int J Mol Sci 23:. 35008465
Wang, P.F., A.A. Jensen, and L. Bunch. (2020). From Methaqualone and Beyond: Structure-Activity Relationship of 6-, 7-, and 8-Substituted 2,3-Diphenyl-quinazolin-4(3)-ones and in Silico Prediction of Putative Binding Modes of Quinazolin-4(3)-ones as Positive Allosteric Modulators of GABA Receptors. ACS Chem Neurosci 11: 4362-4375. 33170625
Wang, Q. and J.W. Lynch. (2012). A comparison of glycine- and ivermectin-mediated conformational changes in the glycine receptor ligand-binding domain. Int J Biochem. Cell Biol. 44: 335-340. 22094187
Wang, S., Q. Liu, X. Li, X. Zhao, L. Qiu, and J. Lin. (2018). Possible binding sites and interactions of propanidid and AZD3043 within the γ-aminobutyric acid type A receptor (GABAR). J Biomol Struct Dyn 36: 3926-3937. 29125020
Wang, W., E.A. Perens, G. Oikonomou, S.W. Wallace, Y. Lu, and S. Shaham. (2017). IGDB-2, an Ig/FNIII protein, binds the ion channel LGC-34 and controls sensory compartment morphogenesis in C. elegans. Dev Biol 430: 105-112. 28803967
Wang, X., A.M. Puinean, A.O. O Reilly, M.S. Williamson, C.L.C. Smelt, N.S. Millar, and Y. Wu. (2017). Mutations on M3 helix of Plutella xylostella glutamate-gated chloride channel confer unequal resistance to abamectin by two different mechanisms. Insect Biochem Mol Biol 86: 50-57. 28576654
Wang, X., R. Wang, Y. Yang, S. Wu, A.O. O''Reilly, and Y. Wu. (2015). A point mutation in the glutamate-gated chloride channel of Plutella xylostella is associated with resistance to abamectin. Insect Mol Biol. [Epub: Ahead of Print] 26592158
Wang, Y., Y.C. Zhang, K.X. Zhang, Z.Q. Jia, T. Tang, L.L. Zheng, D. Liu, and C.Q. Zhao. (2021). Neuroligin 3 from common cutworm enhances the GABA-induced current of recombinant SlRDL1 channel. Pest Manag Sci. [Epub: Ahead of Print] 34619015
Webster, R., S. Maxwell, H. Spearman, K. Tai, O. Beckstein, M. Sansom, and D. Beeson. (2012). A novel congenital myasthenic syndrome due to decreased acetylcholine receptor ion-channel conductance. Brain 135: 1070-1080. 22382357
Wei, Q., S.F. Wu, and C.F. Gao. (2017). Molecular characterization and expression pattern of three GABA receptor-like subunits in the small brown planthopper Laodelphax striatellus (Hemiptera: Delphacidae). Pestic Biochem Physiol 136: 34-40. 28187828
Weiss, S.A. (2023). Chloride ion dysregulation in epileptogenic neuronal networks. Neurobiol Dis 177: 106000. 36638891
Wells, M.M., T.S. Tillman, D.D. Mowrey, T. Sun, Y. Xu, and P. Tang. (2015). Ensemble-based virtual screening for cannabinoid-like potentiators of the human glycine receptor α1 for the treatment of pain. J Med Chem 58: 2958-2966. 25790278
Weltzin, M.M., A.A. George, R.J. Lukas, and P. Whiteaker. (2021). Sleep-related hypermotor epilepsy associated mutations uncover important kinetic roles of α4β2- nicotinic acetylcholine receptor intracellular structures. PLoS One 16: e0247825. 33657187
Westergard, T., R. Salari, J.V. Martin, and G. Brannigan. (2015). Interactions of L-3,5,4''-Triiodothyronine, Allopregnanolone, and Ivermectin with the GABAA Receptor: Evidence for Overlapping Intersubunit Binding Modes. PLoS One 10: e0139072. 26421724
Witzemann, V., E. Stein, B. Barg, T. Konno, M. Koenen, W. Kues, M. Criado, M. Hofmann, and B. Sakmann. (1990). Primary structure and functional expression of the α-, β-, γ-, δ- and ε-subunits of the acetylcholine receptor from rat muscle. Eur J Biochem 194: 437-448. 1702709
Woll, K.A., X. Zhou, N.V. Bhanu, B.A. Garcia, M. Covarrubias, K.W. Miller, and R.G. Eckenhoff. (2018). Identification of binding sites contributing to volatile anesthetic effects on GABA type A receptors. FASEB J. 32: 4172-4189. 29505303
Wu, P., D. Ma, M. Pierzchala, J. Wu, L.C. Yang, X. Mai, X. Chang, and T. Schmidt-Glenewinkel. (2005). The Drosophila acetylcholine receptor subunit D alpha5 is part of an α-bungarotoxin binding acetylcholine receptor. J. Biol. Chem. 280: 20987-20994. 15781463
Wu, Z., R. Lape, L. Jopp-Saile, B.J. O''Callaghan, T. Greiner, and L.G. Sivilotti. (2020). The Startle disease mutation, α1S270T, predicts shortening of glycinergic synaptic currents. J. Physiol. [Epub: Ahead of Print] 32445491
Xiong, W., X. Wu, D.M. Lovinger, and L. Zhang. (2012). A common molecular basis for exogenous and endogenous cannabinoid potentiation of glycine receptors. J. Neurosci. 32: 5200-5208. 22496565
Xue, H. (1998). Identification of major phylogenetic branches of inhibitory ligand-gated channel receptors. J. Mol. Evol. 47: 323-333. 9732459
Yamaguchi, M., Y. Sawa, K. Matsuda, F. Ozoe, and Y. Ozoe. (2012). Amino acid residues of both the extracellular and transmembrane domains influence binding of the antiparasitic agent milbemycin to Haemonchus contortus AVR-14B glutamate-gated chloride channels. Biochem. Biophys. Res. Commun. 419: 562-566. 22369940
Yamato, K., Y. Nakata, M. Takashima, F. Ozoe, M. Asahi, M. Kobayashi, and Y. Ozoe. (2020). Effects of intersubunit amino acid substitutions on GABA receptor sensitivity to the ectoparasiticide fluralaner. Pestic Biochem Physiol 163: 123-129. 31973848
Yang, T., D. Wang, X. Chen, Y. Liang, F. Guo, C. Wu, L. Jia, Z. Hou, W. Li, Z. He, and X. Wang. (2021). F-ASEM Imaging for Evaluating Atherosclerotic Plaques Linked to α7-Nicotinic Acetylcholine Receptor. Front Bioeng Biotechnol 9: 684221. 34277585
Yao, L., M. Wells, X. Wu, Y. Xu, L. Zhang, and W. Xiong. (2020). Membrane cholesterol dependence of cannabinoid modulation of glycine receptor. FASEB J. [Epub: Ahead of Print] 32608538
Yassin, L., B. Gillo, T. Kahan, S. Halevi, M. Eshel, and M. Treinin. (2001). Characterization of the deg-3/des-2 receptor: a nicotinic acetylcholine receptor that mutates to cause neuronal degeneration. Mol. Cell Neurosci 17: 589-599. 11273652
Yévenes, G.E. and H.U. Zeilhofer. (2011). Molecular sites for the positive allosteric modulation of glycine receptors by endocannabinoids. PLoS One 6: e23886. 21901142
Yin, X., G.F. Yang, D.B. Niu, J. Chen, M. Liao, H.Q. Cao, and C.W. Sheng. (2021). Identification and pharmacological characterization of histamine-gated chloride channels in the fall armyworm, Spodoptera frugiperda. Insect Biochem Mol Biol 140: 103698. [Epub: Ahead of Print] 34848284
Yoluk O., Lindahl E. and Andersson M. (2015). Conformational Gating Dynamics in the GluCl Anion-Selective Chloride Channel. ACS Chem Neurosci. 6(8):1459-67. 25992588
Yu, R., H.S. Tae, Q. Xu, D.J. Craik, D.J. Adams, T. Jiang, and Q. Kaas. (2019). Molecular dynamics simulations of dihydro-β-erythroidine bound to the human α4β2 nicotinic acetylcholine receptor. Br J Pharmacol. [Epub: Ahead of Print] 31062355
Yu, X., M. Wang, M. Kang, L. Liu, X. Guo, and B. Xu. (2011). Molecular cloning and characterization of two nicotinic acetylcholine receptor β subunit genes from Apis cerana cerana. Arch Insect Biochem Physiol 77: 163-178. 21618599
Yu, Z., D.C. Chiara, P.Y. Savechenkov, K.S. Bruzik, and J.B. Cohen. (2019). A photoreactive analog of allopregnanolone enables identification of steroid-binding sites in a nicotinic acetylcholine receptor. J. Biol. Chem. [Epub: Ahead of Print] 30923128
Yuan, S., S. Filipek, and H. Vogel. (2016). A Gating Mechanism of the Serotonin 5-HT3 Receptor. Structure 24: 816-825. 27112600
Yuan, X., D. Zhang, S. Mao, and Q. Wang. (2021). Filling the Gap in Understanding the Mechanism of GABAR and Propofol Using Computational Approaches. J Chem Inf Model 61: 1889-1901. 33823589
Zemkova, H., V. Tvrdonova, A. Bhattacharya, and M. Jindrichova. (2014). Allosteric modulation of ligand gated ion channels by ivermectin. Physiol Res 63Suppl1: S215-224. 24564661
Zhan, E., J. Jiang, Y. Wang, K. Zhang, T. Tang, Y. Chen, Z. Jia, Q. Wang, and C. Zhao. (2023). Shisa reduces the sensitivity of homomeric RDL channel to GABA in the two-spotted spider mite, Tetranychus urticae Koch. Pestic Biochem Physiol 192: 105414. 37105623
Zhang, D., M. McGregor, T. Bordia, X.A. Perez, J.M. McIntosh, M.W. Decker, and M. Quik. (2015). α7 nicotinic receptor agonists reduce levodopa-induced dyskinesias with severe nigrostriatal damage. Mov Disord. [Epub: Ahead of Print] 26573698
Zhang, X.L., J.Y. Zhou, P. Zhang, L. Lin, R. Mei, F.L. Zhang, Y.M. Chen, and R. Li. (2023). Clptm1, a new target in suppressing epileptic seizure by regulating GABA R-mediated inhibitory synaptic transmission in a PTZ-induced epilepsy model. Kaohsiung J Med Sci 39: 61-69. 36519412
Zhang, Z.Y., H.H. Bai, Z. Guo, H.L. Li, Y.T. He, X.L. Duan, Z.W. Suo, X. Yang, Y.X. He, and X.D. Hu. (2019). mGluR5/ERK signaling regulated the phosphorylation and function of glycine receptor α1ins subunit in spinal dorsal horn of mice. PLoS Biol 17: e3000371. 31433808
Zheng, F., A.P. Robertson, M. Abongwa, E.W. Yu, and R.J. Martin. (2016). The Ascaris suum nicotinic receptor, ACR-16, as a drug target: Four novel negative allosteric modulators from virtual screening. Int J Parasitol Drugs Drug Resist 6: 60-73. 27054065
Zhu, F. and G. Hummer. (2009). Gating transition of pentameric ligand-gated ion channels. Biophys. J. 97: 2456-2463. 19883588
Zhu, F. and G. Hummer. (2010). Pore opening and closing of a pentameric ligand-gated ion channel. Proc. Natl. Acad. Sci. USA 107: 19814-19819. 21041674
Zhu, S., A. Sridhar, J. Teng, R.J. Howard, E. Lindahl, and R.E. Hibbs. (2022). Structural and dynamic mechanisms of GABA receptor modulators with opposing activities. Nat Commun 13: 4582. 35933426
Zhuang, Y., C.M. Noviello, R.E. Hibbs, R.J. Howard, and E. Lindahl. (2022). Differential interactions of resting, activated, and desensitized states of the α7 nicotinic acetylcholine receptor with lipidic modulators. Proc. Natl. Acad. Sci. USA 119: e2208081119. 36251999
Zouridakis, M., P. Giastas, E. Zarkadas, D. Chroni-Tzartou, P. Bregestovski, and S.J. Tzartos. (2014). Crystal structures of free and antagonist-bound states of human α9 nicotinic receptor extracellular domain. Nat Struct Mol Biol 21: 976-980. 25282151
Zuo, H., L. Gao, Z. Hu, H. Liu, and G. Zhong. (2013). Cloning, expression analysis, and molecular modeling of the γ-aminobutyric acid receptor alpha2 subunit gene from the common cutworm, Spodoptera litura. J Insect Sci 13: 49. 23909412