Voltage-gated sodium channels initiate action potentials in nerve, skeletal muscle, and other electrically excitable cells. Mutations in them cause a wide range of diseases. These channelopathy mutations affect every aspect of sodium channel function, including voltage sensing, voltage-dependent activation, ion conductance, fast and slow inactivation, and both biosynthesis and assembly. Mutations that cause different forms of periodic paralysis in skeletal muscle were discovered first and have provided a template for understanding structure, function, and pathophysiology at the molecular level. More recent work has revealed multiple sodium channelopathies in the brain. Here we review the well-characterized genetics and pathophysiology of the periodic paralyses of skeletal muscle, and then use this information as a foundation for advancing our understanding of mutations in the structurally homologous a subunits of brain sodium channels that cause epilepsy, migraine, autism, and related co-morbidities. We include studies based on molecular and structural biology, cell biology and physiology, pharmacology, and mouse genetics. Our review reveals unexpected connections among these different types of sodium channelopathies.

中文翻译：

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骨骼肌和脑钠通道病

电压门控钠通道在神经、骨骼肌和其他电兴奋细胞中启动动作电位。它们的突变会导致多种疾病。这些通道病突变影响钠通道功能的各个方面，包括电压感应、电压依赖性激活、离子电导、快速和慢速失活，以及生物合成和组装。首先发现了导致骨骼肌不同形式周期性麻痹的突变，并为在分子水平上理解结构、功能和病理生理学提供了模板。最近的工作揭示了大脑中的多种钠离子通道病。在这里，我们回顾了骨骼肌周期性麻痹的充分表征的遗传学和病理生理学，然后使用这些信息作为基础，以促进我们对导致癫痫、偏头痛、自闭症和相关合并症的脑钠通道结构同源 a 亚基突变的理解。我们包括基于分子和结构生物学、细胞生物学和生理学、药理学和小鼠遗传学的研究。我们的审查揭示了这些不同类型的钠离子通道病之间的意想不到的联系。