S1-S3 counter charges in the voltage sensor module of a mammalian sodium channel regulate fast inactivation.

ABSTRACT: The movement of positively charged S4 segments through the electric field drives the voltage-dependent gating of ion channels. Studies of prokaryotic sodium channels provide a mechanistic view of activation facilitated by electrostatic interactions of negatively charged residues in S1 and S2 segments, with positive counterparts in the S4 segment. In mammalian sodium channels, S4 segments promote domain-specific functions that include activation and several forms of inactivation. We tested the idea that S1-S3 countercharges regulate eukaryotic sodium channel functions, including fast inactivation. Using structural data provided by bacterial channels, we constructed homology models of the S1-S4 voltage sensor module (VSM) for each domain of the mammalian skeletal muscle sodium channel hNaV1.

SUBMITTER: Groome JR 

PROVIDER: S-EPMC3639575 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature