Devaux Jérôme J, Kleopa Kleopas A, Cooper Edward C, Scherer Steven S
Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6077, USA.
J Neurosci. 2004 Feb 4;24(5):1236-44. doi: 10.1523/JNEUROSCI.4512-03.2004.
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.
编码钾离子通道KCNQ2的基因突变会导致新生儿癫痫和肌阵挛，这表明KCNQ2分别调节中枢神经系统（CNS）神经元和运动轴突的兴奋性。我们在此表明，KCNQ2通道是轴突起始段和郎飞结的功能组成部分，在整个中枢神经系统和周围神经系统（PNS）中与锚蛋白G和电压依赖性钠离子通道共定位。开放钾离子通道的瑞替加滨会降低轴突兴奋性。阻断钾离子通道的利诺吡啶会延长新生神经动作电位的复极化时间。在发育过程中，KCNQ2在郎飞结和起始段的聚集滞后于锚蛋白G，并且在脑中锚蛋白G和KCNQ2都可以被共免疫沉淀。KCNQ3也是脑中一些起始段和郎飞结的组成部分。突变型KCNQ2通道活性降低是新生儿癫痫和肌阵挛的原因；这些效应的细胞位点可能是轴突起始段和郎飞结。
