Potassium channels

KCa= : calcium-activated potassium channels; Kir= : inward rectifier potassium channels; VGKC, KV= : voltage-gated K+ channels. Potassium (K+) channels have a critical role in cellular signaling in the nervous system. Over the past decade, 50 human genes encoding various K+ channels have been cloned, and there have been important advances in the elucidation of the subunit composition, stoichiometry, biophysical properties, and modulation of these channels. Genetic linkage analyses have led to the identification of many loci encoding K+ channel subunits that are associated with familial epilepsy syndromes as well as other disorders such as episodic ataxia/myokymia, long-QT syndromes, and congenital deafness.1 Antibodies against voltage-gated K+ channels (VGKC, KV) have been associated with autoimmune limbic encephalitis, neuromyotonia, and other neurologic disorders. Over the past several years, there has been increasing interest in developing drugs that modulate the activity of these channels.2 There have been comprehensive reviews on each of these topics.1–7 The focus of this article is on some K+ channels that have been linked with epilepsy. K+ channels are critical in regulation of neuronal excitability, axonal conduction, and neurotransmitter release.1,3–6,8,9 They also have a major role in control of the heart rate and excitability, epithelial electrolyte transport, cell volume regulation, and smooth muscle contraction. Potassium channels are membrane-spanning proteins that selectively allow flow of K+ ions across the cell membrane along their electrochemical gradient. An increase in membrane conductance to K+ ions causes neuronal hyperpolarization, decreases neuronal excitability, and reduces their firing frequency. There is a large number of K+ channels with distinct subcellular localization, biophysical properties, modulation, and pharmacologic profile.1,3,4–9 Potassium channels are polymers of α-subunits encoded by approximately 50 genes in humans. These subunits contain a homologous pore (P) segment selective for K+ ions and a gating mechanism that serves to switch between open and closed channel conformations. …