{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:42:14Z","timestamp":1789605734281,"version":"build-2803163510"},"reference-count":72,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1085\/jgp.201411304","type":"journal-article","created":{"date-parts":[[2015,1,26]],"date-time":"2015-01-26T16:28:31Z","timestamp":1422289711000},"page":"93-106","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":74,"title":["Gating pore currents are defects in common with two Nav1.5 mutations in patients with mixed arrhythmias and dilated cardiomyopathy"],"prefix":"10.1085","volume":"145","author":[{"given":"Adrien","family":"Moreau","sequence":"first","affiliation":[{"name":"Centre de Recherche de L\u2019Institut Universitaire en Sant\u00e9 Mentale de Qu\u00e9bec, Qu\u00e9bec City, Qu\u00e9bec G1J 2G3, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Gosselin-Badaroudine","sequence":"additional","affiliation":[{"name":"Centre de Recherche de L\u2019Institut Universitaire en Sant\u00e9 Mentale de Qu\u00e9bec, Qu\u00e9bec City, Qu\u00e9bec G1J 2G3, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Delemotte","sequence":"additional","affiliation":[{"name":"Institute of Computational Molecular Science, Temple University, Philadelphia, PA 19122 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Computational Molecular Science, Temple University, Philadelphia, PA 19122 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Chahine","sequence":"additional","affiliation":[{"name":"Centre de Recherche de L\u2019Institut Universitaire en Sant\u00e9 Mentale de Qu\u00e9bec, Qu\u00e9bec City, Qu\u00e9bec G1J 2G3, Canada 1"},{"name":"Department of Medicine, Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec G1K 7P4, Canada 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2015,1,26]]},"reference":[{"key":"2023072623313912400_bib1","doi-asserted-by":"publisher","first-page":"21336","DOI":"10.1073\/pnas.1218087109","article-title":"Exploring conformational states of the bacterial voltage-gated sodium channel NavAb via molecular dynamics simulations","volume":"109","author":"Amaral","year":"2012","journal-title":"Proc. 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