2.A.30.1.18
Solute carrier family 12 member 5 (Electroneutral potassium-chloride cotransporter 2) (K-Cl cotransporter 2) (hKCC2) (Neuronal K-Cl cotransporter) of 1139 aas and 12 TMSs. Direct physical coupling between the GABA-A receptor and the KCC2 chloride transporter underlies ionic plasticity in cerebellar purkinje neurons in response to brain-derived neurotrophic factor (BDNF) (Huang et al., 2013).  KCC2 is responsible for maintaining low Cl^- concentrations in neurons of the CNS.  Loss of activity of this transporter provides a mechanism underlying several neurological and psychiatric disorders, including epilepsy, motor spasticity, stress, anxiety, schizophrenia, morphine-induced hyperalgesia and chronic pain (Gagnon et al. 2013).  Mediates chloride extrusion in mature neurons, and it regulates the development and morphology of dendritic spines through structural interactions with the actin cytoskeleton  through interaction with the b isoform of Rac/Cdc42 guanine nucleotide exchange factor, β-PIX (Llano et al. 2015). KCC2 affects the maturation of glycinergic synapses in cultured spinal cord neurons (Schwale et al. 2016). Kainate receptors regulate KCC2 expression in the hippocampus (Pressey et al. 2017). It is is required for neuronal Cl^- homeostasis. As a major extruder of intracellular chloride, it establishes the low neuronal Cl^- levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (Puskarjov et al. 2014). Postnatal changes in expression in the forebrain of mice bearing a mutant nicotinic subunit has been linked to Sleep-Related Epilepsy (Amadeo et al. 2018). KCC2 regulates neuronal excitability and hippocampal activity via interaction with Task-3 channels (Goutierre et al. 2019). Coordinated downregulation of KCC2 and the GABAA receptor contributes to inhibitory dysfunction during seizure induction (Wan et al. 2020).  The expression system influences stability, maturation efficiency, and oligomeric properties of KCC2 (Kok et al. 2024).