Neural KCNQ (Kv7) channels

Br J Pharmacol. 2009 Apr;156(8):1185-95. doi: 10.1111/j.1476-5381.2009.00111.x. Epub 2009 Mar 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholine / metabolism
  • Action Potentials
  • Adrenergic Fibers / metabolism
  • Analgesics / pharmacology
  • Animals
  • Anticonvulsants / pharmacology
  • CA1 Region, Hippocampal / metabolism
  • Humans
  • Ion Channel Gating
  • KCNQ Potassium Channels / drug effects
  • KCNQ Potassium Channels / genetics
  • KCNQ Potassium Channels / metabolism*
  • Muscarinic Agonists / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Potassium / metabolism*
  • Potassium Channel Blockers / pharmacology
  • Pyramidal Cells / metabolism
  • Receptors, Muscarinic / metabolism
  • Sensory Receptor Cells / metabolism
  • Synaptic Transmission* / drug effects


  • Analgesics
  • Anticonvulsants
  • KCNQ Potassium Channels
  • Muscarinic Agonists
  • Potassium Channel Blockers
  • Receptors, Muscarinic
  • Acetylcholine
  • Potassium