Loading...
Gating pore currents are defects in common with two Na<inf>v</inf>1.5 mutations in patients with mixed arrhythmias and dilated cardiomyopathy
Moreau, A Gosselin-Badaroudine, P Delemotte, L Klein, ML Chahine, M
Moreau, A
Gosselin-Badaroudine, P
Delemotte, L
Klein, ML
Chahine, M
Citations
Altmetric:
Genre
Journal Article
Date
2015-01-01
Advisor
Committee member
Group
Department
Permanent link to this record
Collections
Research Projects
Organizational Units
Journal Issue
DOI
10.1085/jgp.201411304
Abstract
© 2015 Moreau et al. The gating pore current, also called omega current, consists of a cation leak through the typically nonconductive voltage-sensor domain (VSD) of voltage-gated ion channels. Although the study of gating pore currents has refined our knowledge of the structure and the function of voltage-gated ion channels, their implication in cardiac disorders has not been established. Two Nav1.5 mutations (R222Q and R225W) located in the VSD are associated with atypical clinical phenotypes involving complex arrhythmias and dilated cardiomyopathy. Using the patch-clamp technique, in silico mutagenesis, and molecular dynamic simulations, we tested the hypothesis that these two mutations may generate gating pore currents, potentially accounting for their clinical phenotypes. Our findings suggest that the gating pore current generated by the R222Q and R225W mutations could constitute the underlying pathological mechanism that links Nav1.5 VSD mutations with human cardiac arrhythmias and dilatation of cardiac chambers.
Description
Citation
Citation to related work
Rockefeller University Press
Has part
Journal of General Physiology
ADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu