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