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The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regulation of neuronal excitability. The M channel is formed by the association of the protein encoded by this gene and a related protein encoded by the KCNQ3 gene, both integral membrane proteins. M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 1 (BFNC), also known as epilepsy, benign neonatal type 1 (EBN1). At least five transcript variants encoding five different isoforms have been found for this gene.[5]
Ligands
ICA-069673: channel opener at KCNQ2/Q3, 20-fold selective over KCNQ3/Q5, no measurable activity against a panel of cardiac ion channels (hERG, Nav1.5, L type channels, and KCNQ1) and no activity on GABAA gated channels at 10 μM. A range of related benzamides exhibited activity, of which compound number 40 is shown here.[6]
Tinel N, Lauritzen I, Chouabe C, Lazdunski M, Borsotto M (November 1998). "The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3". FEBS Letters. 438 (3): 171–6. doi:10.1016/S0014-5793(98)01296-4. PMID9827540. S2CID33708352.
Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D (December 1998). "KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel". Science. 282 (5395): 1890–3. Bibcode:1998Sci...282.1890W. doi:10.1126/science.282.5395.1890. PMID9836639.
Biervert C, Steinlein OK (March 1999). "Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions". Human Genetics. 104 (3): 234–40. doi:10.1007/PL00008713. PMID10323247. S2CID30751027.
Rundfeldt C, Netzer R (March 2000). "The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits". Neuroscience Letters. 282 (1–2): 73–6. doi:10.1016/S0304-3940(00)00866-1. PMID10713399. S2CID28431577.