Uncoupling sodium channel dimers restores the phenotype of a pain-linked Na_v 1.7 channel mutation.

ABSTRACT:

Background and purpose

The voltage-gated sodium channel Na_v 1.7 is essential for adequate perception of painful stimuli. Mutations in the encoding gene, SCN9A, cause various pain syndromes in humans. The hNa_v 1.7/A1632E channel mutant causes symptoms of erythromelalgia and paroxysmal extreme pain disorder (PEPD), and its main gating change is a strongly enhanced persistent current. On the basis of recently published 3D structures of voltage-gated sodium channels, we investigated how the inactivation particle binds to the channel, how this mechanism is altered by the hNa_v 1.7/A1632E mutation, and how dimerization modifies function of the pain-linked mutation.

Experimental approach

We applied atomistic molecular simulations to demonstrate the e

SUBMITTER: Ruhlmann AH 

PROVIDER: S-EPMC7484505 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature