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dc.creatorMoreau, A
dc.creatorGosselin-Badaroudine, P
dc.creatorDelemotte, L
dc.creatorKlein, ML
dc.creatorChahine, M
dc.date.accessioned2021-01-31T16:12:10Z
dc.date.available2021-01-31T16:12:10Z
dc.date.issued2015-01-01
dc.identifier.issn0022-1295
dc.identifier.issn1540-7748
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/5246
dc.identifier.other25624448 (pubmed)
dc.identifier.urihttp://hdl.handle.net/20.500.12613/5264
dc.description.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.
dc.format.extent93-106
dc.language.isoen
dc.relation.haspartJournal of General Physiology
dc.relation.isreferencedbyRockefeller University Press
dc.rightsCC BY-NC-SA
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subjectAmino Acid Sequence
dc.subjectArrhythmias, Cardiac
dc.subjectCardiomyopathy, Dilated
dc.subjectHEK293 Cells
dc.subjectHumans
dc.subjectIon Channel Gating
dc.subjectMolecular Sequence Data
dc.subjectMutation, Missense
dc.subjectNAV1.5 Voltage-Gated Sodium Channel
dc.titleGating pore currents are defects in common with two Na<inf>v</inf>1.5 mutations in patients with mixed arrhythmias and dilated cardiomyopathy
dc.typeArticle
dc.type.genreJournal Article
dc.relation.doi10.1085/jgp.201411304
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.date.updated2021-01-31T16:12:06Z
refterms.dateFOA2021-01-31T16:12:10Z


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