KCNQ2 is a nodal K+ channel.
Mutations in the gene encoding the K+ channel KCNQ2 cause neonatal epilepsy and myokymia, indicating that KCNQ2 regulates the excitability of CNS neurons and motor axons, respectively. We show here that KCNQ2 channels are functional components of axon initial segments and nodes of Ranvier, colocalizing with ankyrin-G and voltage-dependent Na+ channels throughout the CNS and PNS. Retigabine, which opens KCNQ channels, diminishes axonal excitability. Linopirdine, which blocks KCNQ channels, prolongs the repolarization of the action potential in neonatal nerves. The clustering of KCNQ2 at nodes and initial segments lags that of ankyrin-G during development, and both ankyrin-G and KCNQ2 can be coimmunoprecipitated in the brain. KCNQ3 is also a component of some initial segments and nodes in the brain. The diminished activity of mutant KCNQ2 channels accounts for neonatal epilepsy and myokymia; the cellular locus of these effects may be axonal initial segments and nodes.
Devaux
Jérôme J
JJ
Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6077, USA. jdevaux@mail.med.upenn.edu
Kleopa
Kleopas A
KA
Cooper
Edward C
EC
Scherer
Steven S
SS
D019943:Amino Acid Substitution; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D051379:Mice; D009154:Mutation; D020385:Myokymia / Q000235:genetics*; D009900:Optic Nerve / Q000166:cytology / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011233:Precipitin Tests; D011901:Ranvier's Nodes / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
C490613:ANK3 protein, human; C094681:Ank3 protein, mouse; C490614:Ank3 protein, rat; D017487:Ankyrins; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; C496915:Kcnq2 protein, rat; C496917:Kcnq3 protein, mouse; C496918:Kcnq3 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated