ABSTRACT

Voltage gated sodium channels (Na_v) play a crucial role in action potential initiation and propagation. Although the discovery of Na_v channels dates back more than 65 years, and great advances in understanding their localization, biophysical properties, and links to disease have been made, there are still many questions to be answered regarding the cellular and molecular mechanisms involved in Na_v channel trafficking, localization and regulation. This review summarizes the different trafficking mechanisms underlying the polarized Na_v channel localization in neurons, with an emphasis on the axon initial segment (AIS), as well as discussing the latest advances regarding how neurons regulate their excitability by modifying AIS length and location. The importance of Na_v channel localization is emphasized by the relationship between mutations, impaired trafficking and disease. While this review focuses on Na_v1.6, other Na_v isoforms are also discussed.

 抽象的

电压门控钠通道（Na _v ）在动作电位的启动和传播中发挥着至关重要的作用。尽管 Na _v通道的发现可以追溯到 65 多年前，并且在了解其定位、生物物理特性以及与疾病的联系方面已经取得了巨大进展，但关于 Na v 通道所涉及的细胞和分子机制仍有许多问题有待解答。 _v渠道贩运、本地化和监管。这篇综述总结了神经元中极化 Na _v通道定位的不同运输机制，重点是轴突初始段 (AIS)，并讨论了神经元如何通过修改 AIS 长度和位置来调节其兴奋性的最新进展。突变、运输受损和疾病之间的关系强调了 Na _v通道定位的重要性。虽然本综述重点关注 Na _v 1.6，但也讨论了其他 Na _v亚型。