ArticlePflugers Archiv : European journal of physiology2015
Sodium channels in the Cx43 gap junction perinexus may constitute a cardiac ephapse: an experimental and modeling study.
Article in Pflugers Archiv : European journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 155 citations in OpenAlex.
- Monte Carlo modeling of the formation and organization of ion channel clustering.PLoS computational biology · 2026Article
- Heterozygous Loss of Scn1b Results in Concealed Conduction Phenotype Unmasked by Osmotic Stress.bioRxiv : the preprint server for biology · 2026Article
- Phospho-mimic βIII-tubulin rescues microtubule and cardiac defects in Duchenne muscular dystrophy mice.Journal of molecular and cellular cardiology · 2026Article
- Cardiac Impulse Propagation: An Integrated View.JACC. Basic to translational science · 2026Review
- Ephaptic coupling and the source-sink effect of cardiac conduction.The Journal of physiology · 2026Article
- Article
- Dissecting Gap Junctional and Ephaptic Contributions to Electrical Conduction in a Novel Cardiomyocyte Pair Model.bioRxiv : the preprint server for biology · 2026Article
- Gap junctional and ephaptic coupling in cardiac electrical propagation: homocellular and heterocellular perspectives.The Journal of physiology · 2026Review
- Phenotypic Severity ofCirculation. Arrhythmia and electrophysiology · 2026Article
- The influence of intercalated disk nanostructure on local ionic currents and cardiac conduction.Biophysical journal · 2026Article
- Quantifying Early Electromechanical Integration of Cardiomyocytes Using a Minimalist PCL Nanofiber Platform.Polymers · 2025Article
- Analytical Insights into Ephaptic Coupling and Its Effect on Conduction Velocity.Journal of mathematical biology · 2025Article
- SARS-CoV-2 spike protein-induced inflammation underlies proarrhythmia in COVID-19.Scientific reports · 2025Article
- Role of ionic electrodiffusion and ephaptic coupling in cardiac dynamics.Biophysical journal · 2025Article
- Involvement of connexin 43 in myocardial ischemia-reperfusion injury.Cell and tissue research · 2025Review
- Association of ventricular arrhythmias with lamotrigine: an observational cohort study.Scientific reports · 2025Observational
- Intercalated Disc Abnormalities Are Linked to Arrhythmias in Inflammatory Cardiomyopathy.JACC. Clinical electrophysiology · 2025Article
- Article
- Beyond Pulmonary Vein Reconnection: Exploring the Dynamic Pathophysiology of Atrial Fibrillation Recurrence After Catheter Ablation.Journal of clinical medicine · 2025Review
- Ultrastructure and cardiac impulse propagation: scaling up from microscopic to macroscopic conduction.The Journal of physiology · 2025Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
It has long been held that electrical excitation spreads from cell-to-cell in the heart via low resistance gap junctions (GJ). However, it has also been proposed that myocytes could interact by non-GJ-mediated "ephaptic" mechanisms, facilitating propagation of action potentials in tandem with direct GJ-mediated coupling. We sought evidence that such mechanisms contribute to cardiac conduction. Using super-resolution microscopy, we demonstrate that Nav1.5 is localized within 200 nm of the GJ plaque (a region termed the perinexus). Electron microscopy revealed close apposition of adjacent cell membranes within perinexi suggesting that perinexal sodium channels could function as an ephapse, enabling ephaptic cell-to-cell transfer of electrical excitation. Acute interstitial edema (AIE) increased intermembrane distance at the perinexus and was associated with preferential transverse conduction slowing and increased spontaneous arrhythmia incidence. Inhibiting sodium channels with 0.5 μM flecainide uniformly slowed conduction, but sodium channel inhibition during AIE slowed conduction anisotropically and increased arrhythmia incidence more than AIE alone. Sodium channel inhibition during GJ uncoupling with 25 μM carbenoxolone slowed conduction anisotropically and was also highly proarrhythmic. A computational model of discretized extracellular microdomains (including ephaptic coupling) revealed that conduction trends associated with altered perinexal width, sodium channel conductance, and GJ coupling can be predicted when sodium channel density in the intercalated disk is relatively high. We provide evidence that cardiac conduction depends on a mathematically predicted ephaptic mode of coupling as well as GJ coupling. These data suggest opportunities for novel anti-arrhythmic therapies targeting noncanonical conduction pathways in the heart.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.