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• W1736719008 endingPage "1195" @default.
• W1736719008 startingPage "1185" @default.
• W1736719008 abstract "KCNQ genes encode five Kv7 K(+) channel subunits (Kv7.1-Kv7.5). Four of these (Kv7.2-Kv7.5) are expressed in the nervous system. Kv7.2 and Kv7.3 are the principal molecular components of the slow voltage-gated M-channel, which widely regulates neuronal excitability, although other subunits may contribute to M-like currents in some locations. M-channels are closed by receptors coupled to Gq such as M1 and M3 muscarinic receptors; this increases neuronal excitability and underlies some forms of cholinergic excitation. Muscarinic closure results from activation of phospholipase C and consequent hydrolysis and depletion of membrane phosphatidylinositol-4,5-bisphosphate, which is required for channel opening. Some effects of M-channel closure, determined from transmitter action, selective blocking drugs (linopirdine and XE991) and KCNQ2 gene disruption or manipulation, are as follows: (i) in sympathetic neurons: facilitation of repetitive discharges and conversion from phasic to tonic firing; (ii) in sensory nociceptive systems: facilitation of A-delta peripheral sensory fibre responses to noxious heat; and (iii) in hippocampal pyramidal neurons: facilitation of repetitive discharges, enhanced after-depolarization and burst-firing, and induction of spontaneous firing through a reduction of action potential threshold at the axon initial segment. Several drugs including flupirtine and retigabine enhance neural Kv7/M-channel activity, principally through a hyperpolarizing shift in their voltage gating. In consequence they reduce neural excitability and can inhibit nociceptive stimulation and transmission. Flupirtine is in use as a central analgesic; retigabine is under clinical trial as a broad-spectrum anticonvulsant and is an effective analgesic in animal models of chronic inflammatory and neuropathic pain." @default.
• W1736719008 created "2016-06-24" @default.
• W1736719008 creator A5010524977 @default.
• W1736719008 creator A5027714194 @default.
• W1736719008 date "2009-04-06" @default.
• W1736719008 modified "2023-10-14" @default.
• W1736719008 title "Neural KCNQ (Kv7) channels" @default.
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• W1736719008 doi "https://doi.org/10.1111/j.1476-5381.2009.00111.x" @default.
• W1736719008 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2697739" @default.
• W1736719008 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19298256" @default.
• W1736719008 hasPublicationYear "2009" @default.
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