Cooper Edward C
Departments of Neurology and Neuroscience, Baylor College of Medicine, Houston, TX, USA
Potassium ion (K) channels are implicated in epilepsy by their physiology, genetics, and pharmacology. K channels are ubiquitous in neuronal and glial cell membranes. They are central to excitability, considered at the level of the subcellular domain, individual cell, or circuit. K channels play a major part in setting the inward-negative resting membrane potential. They enable glial extracellular K buffering, and shape depolarizations caused by excitatory synaptic inputs or action potentials in dendritic spines and shafts, somata, axons, and presynaptic terminals. Some K channel subtypes reduce excitability, delaying the onset or limiting the number of action potentials following an excitatory input. Others exert seemingly opposite effects, promoting rapid neuronal firing by hastening spike repolarization and the recovery of sodium (Na) channels from inactivation. Many subtypes are convergently regulated by membrane receptors, intracellular signal pathways, and 2 messengers, thereby integrating metabolism and excitability. K channel diversity depends on the expression of an exceptionally large number of genes encoding principal (pore-forming) and accessory (non-pore-forming) subunits. Several K channel genes are mutated in inherited epilepsy in humans and non-human model animals. Many experimental proconvulsants bind and block K channels; others inhibit K+ channels indirectly via intracellular messengers. Conversely, openers of one K channel subfamily, alternatively called the KCNQ, Kv7, or M-channels, have emerged as a novel class of anti-epileptic drugs.
钾离子（K⁺）通道在生理、遗传和药理学方面均与癫痫有关。钾通道广泛存在于神经元和神经胶质细胞膜中。它们在兴奋性方面起着核心作用，无论是在亚细胞结构域、单个细胞还是神经回路层面来看都是如此。钾通道在设定内向负性静息膜电位方面发挥着主要作用。它们能够实现神经胶质细胞对细胞外钾离子的缓冲作用，并塑造由兴奋性突触输入或树突棘、树突干、胞体、轴突和突触前终末处的动作电位所引起的去极化。一些钾通道亚型会降低兴奋性，延迟兴奋性输入后动作电位的起始或限制其数量。其他亚型则产生看似相反的作用，通过加速峰电位复极化以及使钠（Na⁺）通道从失活状态恢复来促进神经元快速放电。许多亚型受到膜受体、细胞内信号通路和第二信使的共同调节，从而整合代谢与兴奋性。钾通道的多样性取决于大量编码主要（形成孔道的）和辅助（非形成孔道的）亚基的基因的表达。在人类和非人类模式动物的遗传性癫痫中，有几个钾通道基因发生了突变。许多实验性惊厥剂会结合并阻断钾通道；其他一些则通过细胞内信使间接抑制钾离子通道。相反，一类新型抗癫痫药物已出现，它们是一个钾通道亚家族的开放剂，也被称为KCNQ、Kv7或M通道。
