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Prog Biophys Mol Biol. 2019 Jul;144:41-50. doi: 10.1016/j.pbiomolbio.2018.08.003. Epub 2018 Sep 19.

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

Author information

1
Virginia Tech Carilion Research Institute, Roanoke, VA, USA.
2
Department of Chemistry, Blacksburg, VA, USA.
3
Virginia Tech Carilion Research Institute, Roanoke, VA, USA; Department of Biomedical Engineering and Mechanics, Blacksburg, VA, USA.
4
Virginia Tech Carilion Research Institute, Roanoke, VA, USA; Department of Biomedical Engineering and Mechanics, Blacksburg, VA, USA; Department of Emergency Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA. Electronic address: gourdier@vtc.vt.edu.

Abstract

Cardiovascular 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 β subunit (Scn1b) may be a novel anti-arrhythmic target.

KEYWORDS:

Arrhythmia; Conduction; Ephaptic; Gap junctions; Heart; Na(V)1.5/Scn5a; Perinexus; β1/Scn1b

PMID:
30241906
PMCID:
PMC6422736
[Available on 2020-07-01]
DOI:
10.1016/j.pbiomolbio.2018.08.003
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