1.A.1.15.3
6 TMS voltage-gated K⁺ channel, KCNQ3 or K_v7.3.  Mutations cause benign familial neonatal convulsions (BNFC; epilepsy; Maljevic et al. 2016). Forms homotetramers or heterotetramers with KCNQ2 (Soldovieri et al., 2006; Uehara et al., 2008).  Retigabine and ICA73, two anti-epileptic drugs, act via distinct mechanisms due to interactions with specific residues that underlie subtype specificity of KCNQ channel openers (Wang et al. 2016). Gabapentin at low concentrations is a activator of KCNQ3, KCNQ2/3 and KCNQ5 but not KCNQ2 or KCNQ4 (Manville and Abbott 2018). At high concentrations it can be inhibitory.  A  tight spatial and functional relationship between the DAT/GLT-1 transporters and the Kv7.2/7.3 potassium channel immediately readjusts the membrane potential of the neuron, probably to limit the neurotransmitter-mediated neuronal depolarization (Bartolomé-Martín et al. 2019). E-2-dodecenal from cilantro (Coriandrum sativum) is a potent activator and anticonvulsant that binds with an affinity of 60 nM to TMS5 in several KCNQ channels including KCNQ2 and 3 (Manville and Abbott 2019). Pathogenic variants in KCNQ2 and KCNQ3, paralogous genes encoding Kv7.2 and Kv7.3 voltage-gated K⁺ channel subunits, are responsible for early-onset developmental/epileptic disorders characterized by heterogeneous clinical phenotypes ranging from benign familial neonatal epilepsy (BFNE) to early-onset developmental and epileptic encephalopathy (DEE). KCNQ2 variants account for the majority of pedigrees with BFNE, and KCNQ3 variants are responsible for a much smaller subgroup (Miceli et al. 2020). The M240R variant mainly affects the voltage sensitivity, in contrast to previously analyzed BFNE Kv7.3 variants that reduce current density (Miceli et al. 2020).