Regulation of Na⁺ channel inactivation by the DIII and DIV voltage-sensing domains.

ABSTRACT: Functional eukaryotic voltage-gated Na⁺ (Na_V) channels comprise four domains (DI-DIV), each containing six membrane-spanning segments (S1-S6). Voltage sensing is accomplished by the first four membrane-spanning segments (S1-S4), which together form a voltage-sensing domain (VSD). A critical Na_V channel gating process, inactivation, has previously been linked to activation of the VSDs in DIII and DIV. Here, we probe this interaction by using voltage-clamp fluorometry to observe VSD kinetics in the presence of mutations at locations that have been shown to impair Na_V channel inactivation. These locations include the DIII-DIV linker, the DIII S4-S5 linker, and the DIV S4-S5 linker. Our results show that, within the 10-ms timeframe of fast inactivati

SUBMITTER: Hsu EJ 

PROVIDER: S-EPMC5339511 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature