Cannon Stephen C
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Annu Rev Neurosci. 2006;29:387-415. doi: 10.1146/annurev.neuro.29.051605.112815.
Ion channelopathies are a diverse array of human disorders caused by mutations in ion channel genes. This review focuses on the pathogenic mechanisms of channelopathies affecting skeletal muscle and brain arising from mutations of voltage-gated ion channels and fast ligand-gated ion channels expressed at the surface membrane. Derangements in channel function alter the electrical excitability of the cell and thereby increase susceptibility to transient symptomatic attacks including myasthenia, periodic paralysis, myotonic stiffness, seizures, headache, dyskinesia, or episodic ataxia. Although these disorders are rare, they stand out as exemplary cases for which disease pathogenesis can be traced from a point mutation to altered protein function, to altered cellular activity, and to clinical phenotype. The study of these disorders has provided insights on channel structure-function relations, the physiological roles of ion channels, and rational approaches toward therapeutic intervention for many disorders of cellular excitability.
离子通道病是由离子通道基因突变引起的一系列多样的人类疾病。本综述重点关注由电压门控离子通道和表达于表面膜的快速配体门控离子通道突变所引发的、影响骨骼肌和大脑的通道病的致病机制。通道功能紊乱会改变细胞的电兴奋性，从而增加对包括肌无力、周期性瘫痪、肌强直、癫痫发作、头痛、运动障碍或发作性共济失调等短暂症状性发作的易感性。尽管这些疾病较为罕见，但它们作为典型案例脱颖而出，其疾病发病机制能够从点突变追溯到蛋白质功能改变、细胞活性改变以及临床表型。对这些疾病的研究为通道结构 - 功能关系、离子通道的生理作用以及针对许多细胞兴奋性紊乱的治疗干预合理方法提供了见解。
