Distinct modulation of inactivation by a residue in the pore domain of voltage-gated Na⁺ channels: mechanistic insights from recent crystal structures.

ABSTRACT: Inactivation of voltage-gated Na⁺ channels (VGSC) is essential for the regulation of cellular excitability. The molecular rearrangement underlying inactivation is thought to involve the intracellular linker between domains III and IV serving as inactivation lid, the receptor for the lid (domain III S4-S5 linker) and the pore-lining S6 segements. To better understand the role of the domain IV S6 segment in inactivation we performed a cysteine scanning mutagenesis of this region in rNav 1.4 channels and screened the constructs for perturbations in the voltage-dependence of steady state inactivation. This screen was performed in the background of wild-type channels and in channels carrying the mutation K1237E, which profoundly alters both permeation and gating-properties. Of all te

SUBMITTER: Cervenka R 

PROVIDER: S-EPMC5766632 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature