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