KV7.2 channels

Channel name Kv7.2
Description Voltage-gated potassium channel, delayed rectifier
Other names KQT2
Molecular information Human: 872aa, NM_172107 (transcript variant 1), chr. 20q13.3, KCNQ2, GeneID: 3785, PMID: 98366391
Mouse: 870aa, NM_010611 (transcript variant 1), chr. 2
Rat: 852aa, NM_133322, chr. 3q43
Associated subunits KCNQ3, KCNE2
Functional assays Voltage-clamp
Current M current
Conductance 5.8pS13
Ion selectivity K+
Activation Va = 26 mV, τa = 157 ms at +30 mV
Inactivation Vh = 18 mV, τh = 130 ms at 20 mV
Activators Retigabine (10 μM),2 BMS204352 (1 μM)3
Gating inhibitors None
Blockers Tetraethyammonium (KCNQ2 alone: 0.16 mM; KCNQ2/KCNQ3: 0.5 mM),1 XE991 (0.7 μM),1,4 linopiridine (4.8 μM),1,3 L735821 (1.5 μM)5
Radioligands None
Channel distribution Infant brain, adult brain, fetal brain, sympathetic ganglia, lung, testis, fetal heart, adult heart, breast, eye, germ cell, placenta, small intestine, neuroblastoma10
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 hippocampus11; KCNQ2 is also expressed in the absence of KCNQ3 in some presynaptic terminals11
Mutations and pathophysiology Benign familial neonatal convulsions (EBN1) with myokymia6,7; in KCNQ2 knockout mice, homozygotes (KCNQ2—/—) die within a few hours after birth owing to pulmonary atelectasis that is not due to the status of epileptic seizures, although their development is morphologically normal; heterozygous mice have decreased expression of KCNQ2 and show hypersensitivity to pentylenetetrazole, an inducer of seizure12
Pharmacological significance Retigabine is an anticonvulsant2 (the M current is a new target for antiepileptic therapy8,9; blockers enhance learning and memory in animal models9
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; BMS204352, 3-(5-chloro-2-methoxy-phenyl)-3-fluoro-6-(trifluoromethyl)-1H-indol-2- one; XE991, 10,10-bis(pyridin-4-ylmethyl)anthracen-9-one; L735821, 3-(2,4-dichlorophenyl)-N-(6-methyl-5-oxo-2-phenyl-3,6-diazabicyclo[5. 4.0]undeca-2,7,9,11-tetraen-4-yl)-prop-2-enamide.

  • 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. Tatulian L, Delmas P, Abogadie FC, and Brown DA (2001). Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine. J Neurosci 21:5535-5545

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

  • 4. Robbins J (2001) KCNQ potassium channels: physiology, pathophysiology, and pharmacology. Pharmacol Ther 90:1-19

  • 5. Tinel N, Lauritzen I, Chouabe C, Lazdunski M, and Borsotto M (1998) The KCNQ2 potassium channel: splice variants, functional and develo pMental expression: brain localization and comparison with KCNQ3. FEBS Lett. 438:171-176

  • 6. Charlier C, Singh NA, Ryan SG, Lewis TB, Reus BE, Leach R, 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

  • 7. Biervert C, Schroeder BC, Kubisch C, Berkovic CF, Propping P, Jentsch TJ, and Steinlein OK (1998) A potassium channel mutation in neonatal human epilepsy Science (Wash DC) 279:403-406

  • 8. Cooper EC (2001) Potassium channels: how genetic studies of epileptic syndromes open paths to new therapeutic targets and drugs. Epilepsia 42:49-54

  • 9. 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

  • 10. 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

  • 11. 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

  • 12. Watanabe H, Nagata E, Kosakai A, Nakamura M, Yokoyama M, Tanaka K, and Sasai H (2000) Disruption of the epilepsy KCNQ2 gene results in neural hyperexcitability. J Neurochem 75:28-33

  • 13. Selyanko AA, Hadley JK, Wood IC, Abogadie FC, Delmas P, Buckley NJ, London B, and Brown DA (2001) Properties of single M-type KCNQ2/KCNQ3 potassium channels expressed in mammalian cells. J Physiol 534:15-24