Pei Zifan, Pan Yanling, Cummins Theodore R
Department of Biology, Indiana University - Purdue University Indianapolis, Indianapolis, IN, USA.
Department of Pharmacology and Toxicology, Indiana University - Purdue University Indianapolis, Indianapolis, IN, USA.
Handb Exp Pharmacol. 2018;246:101-124. doi: 10.1007/164_2017_69.
Voltage-gated sodium channels (VGSCs) are critical determinants of excitability. The properties of VGSCs are thought to be tightly controlled. However, VGSCs are also subjected to extensive modifications. Multiple posttranslational modifications that covalently modify VGSCs in neurons and muscle have been identified. These include, but are not limited to, phosphorylation, ubiquitination, palmitoylation, nitrosylation, glycosylation, and SUMOylation. Posttranslational modifications of VGSCs can have profound impact on cellular excitability, contributing to normal and abnormal physiology. Despite four decades of research, the complexity of VGSC modulation is still being determined. While some modifications have similar effects on the various VGSC isoforms, others have isoform-specific interactions. In addition, while much has been learned about how individual modifications can impact VGSC function, there is still more to be learned about how different modifications can interact. Here we review what is known about VGSC posttranslational modifications with a focus on the breadth and complexity of the regulatory mechanisms that impact VGSC properties.
电压门控钠通道（VGSCs）是兴奋性的关键决定因素。人们认为VGSCs的特性受到严格控制。然而，VGSCs也会经历广泛的修饰。已经确定了多种在神经元和肌肉中对VGSCs进行共价修饰的翻译后修饰。这些修饰包括但不限于磷酸化、泛素化、棕榈酰化、亚硝基化、糖基化和SUMO化。VGSCs的翻译后修饰可对细胞兴奋性产生深远影响，有助于正常和异常生理过程。尽管经过了四十年的研究，但VGSC调节的复杂性仍在不断明确。虽然一些修饰对各种VGSC亚型有相似的影响，但其他修饰则具有亚型特异性相互作用。此外，虽然我们已经对单个修饰如何影响VGSC功能有了很多了解，但对于不同修饰如何相互作用仍有更多需要了解的地方。在这里，我们回顾关于VGSC翻译后修饰的已知信息，重点关注影响VGSC特性的调节机制的广度和复杂性。
