文章基本信息

标题：Synergetic Action of Domain II and IV Underlies Persistent Current Generation in Na_v1.3 as revealed by a tarantula toxin
本地全文：下载
作者：Cheng Tang ; Xi Zhou ; Yunxiao Zhang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep09241
出版社：Springer Nature
摘要：The persistent current (I_NaP) through voltage-gated sodium channels enhances neuronal excitability by causing prolonged depolarization of membranes. Na_v1.3 intrinsically generates a small I_NaP, although the mechanism underlying its generation remains unclear. In this study, the involvement of the four domains of Na_v1.3 in I_NaP generation was investigated using the tarantula toxin α-hexatoxin-MrVII (RTX-VII). RTX-VII activated Na_v1.3 and induced a large I_NaP. A pre-activated state binding model was proposed to explain the kinetics of toxin-channel interaction. Of the four domains of Na_v1.3, both domain II and IV might play important roles in the toxin-induced I_NaP. Domain IV constructed the binding site for RTX-VII, while domain II might not participate in interacting with RTX-VII but could determine the efficacy of RTX-VII. Our results based on the use of RTX-VII as a probe suggest that domain II and IV cooperatively contribute to the generation of I_NaP in Na_v1.3.