Menezes Luis Felipe Santos, Sabiá Júnior Elias Ferreira, Tibery Diogo Vieira, Carneiro Lilian Dos Anjos, Schwartz Elisabeth Ferroni
Laboratório de Neurofarmacologia, Departamento de Ciências Fisiológicas, Universidade de Brasília, Brasília, Brazil.
Faculdade de Medicina, Centro Universitário Euro Americano, Brasília, Brazil.
Front Pharmacol. 2020 Aug 18;11:1276. doi: 10.3389/fphar.2020.01276. eCollection 2020.
Epilepsy is a disease characterized by abnormal brain activity and a predisposition to generate epileptic seizures, leading to neurobiological, cognitive, psychological, social, and economic impacts for the patient. There are several known causes for epilepsy; one of them is the malfunction of ion channels, resulting from mutations. Voltage-gated sodium channels (NaV) play an essential role in the generation and propagation of action potential, and malfunction caused by mutations can induce irregular neuronal activity. That said, several genetic variations in NaV channels have been described and associated with epilepsy. These mutations can affect channel kinetics, modifying channel activation, inactivation, recovery from inactivation, and/or the current window. Among the NaV subtypes related to epilepsy, NaV1.1 is doubtless the most relevant, with more than 1500 mutations described. Truncation and missense mutations are the most observed alterations. In addition, several studies have already related mutated NaV channels with the electrophysiological functioning of the channel, aiming to correlate with the epilepsy phenotype. The present review provides an overview of studies on epilepsy-associated mutated human NaV1.1, NaV1.2, NaV1.3, NaV1.6, and NaV1.7.
癫痫是一种以大脑异常活动为特征且易引发癫痫发作的疾病，会给患者带来神经生物学、认知、心理、社会和经济方面的影响。癫痫有多种已知病因，其中之一是由突变导致的离子通道功能异常。电压门控钠通道（NaV）在动作电位的产生和传播中起关键作用，突变引起的功能异常可诱发神经元活动异常。也就是说，已描述了NaV通道中的几种基因变异，并将其与癫痫相关联。这些突变可影响通道动力学，改变通道激活、失活、从失活状态恢复以及/或者电流窗口。在与癫痫相关的NaV亚型中，NaV1.1无疑是最相关的，已描述了1500多种突变。截短突变和错义突变是最常见的改变。此外，多项研究已将突变的NaV通道与通道的电生理功能相关联，旨在与癫痫表型建立关联。本综述概述了与癫痫相关的人类突变型NaV1.1、NaV1.2、NaV1.3、NaV1.6和NaV1.7的研究。
