KV7.3 channels

Channel name Kv7.3
Description Voltage-gated potassium channel, delayed rectifier
Other names None
Molecular information Human: 872aa NM_004519, chr. 8q24, KCNQ3, GeneID: 3786, PMID: 98366391
Mouse: 873aa, NM_152923, chr. 15
Rat: 873aa, NM_031597, chr. 7q33
Associated subunits KCNQ2, KCNQ5
Functional assays Voltage-clamp
Current M current1
Conductance 7.3pS
Ion selectivity K+
Activation Va = 39 mV, τa = 60 ms at +30 mV
Inactivation Not established
Activators Retigabine (KCNQ3 alone: 0.6 μM; KCNQ3/KCNQ5: 1.4 μM)2; XE991,3 BMS204352 (1 μM)4
Gating inhibitors None
Blockers Tetraethyammonium (>30 mM),5 linopiridine (KCNQ3/KCNQ5: 7.7 μM)2
Radioligands None
Channel distribution Brain, testis, retina, colon, eye, head, neck
Physiological functions Determines subthreshold excitability of neurons; KCNQ2 and KCNQ3 coassemble to form the M current in the brain1 (see “Comments”); KCNQ2 and KCNQ3 proteins are colocalized in a somatodendritic pattern on pyramidal and polymorphic neurons in the human cortex and hippocampus7,8
Mutations and pathophysiology Benign familial neonatal convulsions (EBN2) (e.g., G263V mutation in the pore)9
Pharmacological significance Anticonvulsants (activators), cognition enhancers (blockers)6
Comments The M current is a slowly activating and deactivating potassium conductance that plays a critical role in determining the subthreshold excitability of neurons as well as the responsiveness to synaptic inputs; the M current was first described in peripheral sympathetic neurons, and differential expression of this conductance produces subtypes of sympathetic neurons with distinct firing patterns; the M current is also expressed in many neurons in the central nervous system
  • aa, amino acids; chr., chromosome; XE991 10,10-bis(pyridin-4-ylmethyl)anthracen-9-one; BMS204352, 3-(5-chloro-2-methoxy-phenyl)-3-fluoro-6-(trifluoromethyl)-1H-indol-2-one.

  • 1. Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, and McKinnon D (1998) KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science (Wash DC) 282:1890-1893

  • 2. Wickenden AD, Zou A, Wagoner PK, and Jegla T (2001) Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells. Br. J. Pharmacol 132:381-384

  • 3. Wang HS, Brown BS, McKinnon D, and Cohen IS (2000) Molecular basis for differential sensitivity of KCNQ, and IKs channels to the cognitive enhancer XE991. Mol Pharmacol 57:1218-1223

  • 4. Schroder RL, Jespersen T, Christophersen P, Strobaek D, Jensen BS, and Olesen SP (2001) KCNQ4 channel activation by BMS-204352 and retigabine. Neuropharmacology 40:888-898

  • 5. Hadley JK, Noda M, Selyanko AA, Wood IC, Abogadie FC, and Brown DA (2000) Differential tetraethylammonium sensitivity of KCNQ1–4 potassium channels. Br J Pharmacol 129:413-415

  • 6. Coghlan MJ, Carroll WA, and Gopalakrishnan M (2001) Recent develo pMents in the biology and medicinal chemistry of potassium channel modulators: update from a decade of progress. J Med Chem 44:1627-1653

  • 7. Smith JS, Iannotti C, Dargis P, Christian EP, and Aiyar J (2001) Differential expression of KCNQ2 splice variants: implications to M current function during neuronal develo pMent. J Neurosci 21:1096-1103

  • 8. Cooper EC, Aldape KD, Abosch A, Barbaro NM, Berger MS, Peacock WS, Jan YN, and Jan LY (2000) Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. Proc Natl Acad Sci USA 97:4914-4919

  • 9. Charlier C, Singh NA, Ryan SG, Lewis TB, Reus BE, Leach RJ, and Leppert M (1998) A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nat Genet 18:53-55