The role of the gap junction perinexus in cardiac conduction: Potential as a novel anti-arrhythmic drug target

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dc.contributor.authorHoagland, Daniel T.en
dc.contributor.authorSantos, Webster L.en
dc.contributor.authorPoelzing, Stevenen
dc.contributor.authorGourdie, Robert G.en
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentChemistryen
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.date.accessioned2020-09-01T17:47:22Zen
dc.date.available2020-09-01T17:47:22Zen
dc.date.issued2018-09-19en
dc.description.abstractCardiovascular disease remains the single largest cause of natural death in the United States, with a significant cause of mortality associated with cardiac arrhythmias. Presently, options for treating and preventing myocardial electrical dysfunction, including sudden cardiac death, are limited. Recent studies have indicated that conduction of electrical activation in the heart may have an ephaptic component, wherein intercellular coupling occurs via electrochemical signaling across narrow extracellular clefts between cardiomyocytes. The perinexus is a 100-200 nm-wide stretch of closely apposed membrane directly adjacent to connexin 43 gap junctions. Electron and super-resolution microscopy studies, as well as biochemical analyses, have provided evidence that perinexal nanodomains may be candidate structures for facilitating ephaptic coupling. This work has included characterization of the perinexus as a region of close inter-membrane contact between cardiomyocytes (<30 nm) containing dense clusters of voltage-gated sodium channels. Here, we review what is known about perinexal structure and function and the potential that the perinexus may have novel and pivotal roles in disorders of cardiac conduction. Of particular interest is the prospect that cell adhesion mediated by the cardiac sodium channel b subunit (Scn1b) may be a novel anti-arrhythmic target.en
dc.format.extent10 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttp://hdl.handle.net/10919/99879en
dc.identifier.volume144en
dc.language.isoenen
dc.publisherElsevieren
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectGap junctionsen
dc.subjectPerinexusen
dc.subjectHearten
dc.subjectConductionen
dc.subjectArrhythmiaen
dc.subjectEphapticen
dc.subjectNaV1.5/Scn5aen
dc.subjectβ1/Scn1ben
dc.titleThe role of the gap junction perinexus in cardiac conduction: Potential as a novel anti-arrhythmic drug targeten
dc.title.serialProgress in Biophysics and Molecular Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Scholarly Works, Fralin Biomedical Research Institute at VTC
Scholarly Works, Biomedical Engineering and Mechanics
Scholarly Works, Chemistry
Scholarly Works, Virginia Tech Carilion School of Medicine (VTCSOM)