Voltage-Gated Sodium Channels: Mutations, Channelopathies and Targets
Abstract:Voltage-gated sodium channels produce fast depolarization, which is responsible for the rising phase of the action potential in neurons, muscles and heart. These channels are very large membrane proteins and are encoded by ten genes in mammals. Sodium channels are a crucial component of excitable tissues; hence, they are a target for various neurotoxins that are produced by plants and animals for defence and protection, such as tetrodotoxin, scorpion toxins and batrachotoxin. Several mutations in various sodium channel subtypes cause multiple inherited diseases known as channelopathies. When these mutated sodium channel subtypes are expressed in various tissues, channelopathies in brain, skeletal muscle and cardiac muscle develop as well as neuropathic pain. In this review, we discuss aspects of voltage-gated sodium channel genes with an emphasis on cardiac muscle sodium channels. In addition, we report novel mutations that underlie a spectrum of diseases, such as Brugada, long QT syndrome and inherited conduction disorders. Furthermore, this review explains commonalities and differences among the channel subtypes, the channelopathies caused by the sodium channel gene mutation and the specificity of toxins and blockers of the channel subtypes.
Keywords: Atrial Fibrillation; CHANNELOPATHIES; Coding exons; Drosophila; Epilepsy Associated; Infant; Neuropathic Pain; Scorpion Toxins; Sick Sinus Syndrome; Toxins; Voltage-gated sodium channel; antiepileptic drugs; aromatic tyrosine; arrhythmic syndromes; atrial fibrillation; atrial standstill; cardiac cells [41-4; cardiac death; celectrocardiogram; cell adhesion; channel trafficking; channel-selective blocker; channelopathy; chromosome; complex multimeric structure; density; depolarization; febrile seizure; fibrillation; ganglion; gating modulation; glutamic acid; heterologous expression system; hreshold channel; hyperpolarization-activated; hypoexcitability; hypokalemic periodic paralysis; insecticide pyrethroids; ion selectivity; mammalian isoforms; microglial cells; micromolar; modifying -subunits; myotonia; myotonia fluctuans; neonatal-infantile seizure; pacemaker; pain; paralysis; paramyotonia congenita; phenylalanine; phosphorylation; polar; potassium-aggravated myotonia; scorpion venom; sinoatrial; sinus node dysfunction; skeletal muscle; sodium channel mutations; sodium channel subtypes; stability of the membrane; subtype selective sodium channel blockers; subtype selective sodium channel toxins; tachyarrhythmia; tachycardia-bradycardia syndrome; trigeminal ganglia; two hydrophobic; ventricular myocar-dium; ventricular tachycardia
Document Type: Research Article
Publication date: January 1, 2011
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