Mechanisms of noncovalent β subunit regulation of Na_V channel gating.

ABSTRACT: Voltage-gated Na⁺ (Na_V) channels comprise a macromolecular complex whose components tailor channel function. Key components are the non-covalently bound β1 and β3 subunits that regulate channel gating, expression, and pharmacology. Here, we probe the molecular basis of this regulation by applying voltage clamp fluorometry to measure how the β subunits affect the conformational dynamics of the cardiac Na_V channel (Na_V1.5) voltage-sensing domains (VSDs). The pore-forming Na_V1.5 α subunit contains four domains (DI-DIV), each with a VSD. Our results show that β1 regulates Na_V1.5 by modulating the DIV-VSD, whereas β3 alters channel kinetics mainly through DIII-VSD interaction. Introduction of a quenching tryptophan into the extra

SUBMITTER: Zhu W 

PROVIDER: S-EPMC5560778 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature