ArticleAmerican journal of physiology. Heart and circulatory physiology2016
Extracellular sodium dependence of the conduction velocity-calcium relationship: evidence of ephaptic self-attenuation.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 43 citations in OpenAlex.
- In silico predictions of action potential propagation in doxorubicin cardiotoxicity: A parametric study using preclinical 3D magnetic resonance imaging-based fibrotic left ventricle models.The Journal of physiology · 2026Article
- Heterozygous Loss of Scn1b Results in Concealed Conduction Phenotype Unmasked by Osmotic Stress.bioRxiv : the preprint server for biology · 2026Article
- Cardiac Impulse Propagation: An Integrated View.JACC. Basic to translational science · 2026Review
- Gap junctional and ephaptic coupling in cardiac electrical propagation: homocellular and heterocellular perspectives.The Journal of physiology · 2026Review
- Analytical Insights into Ephaptic Coupling and Its Effect on Conduction Velocity.Journal of mathematical biology · 2025Article
- Role of ionic electrodiffusion and ephaptic coupling in cardiac dynamics.Biophysical journal · 2025Article
- Age-Associated Perinexal Narrowing Masks Consequences of Sodium Channel Gain of Function in Guinea Pig Hearts.JACC. Clinical electrophysiology · 2025Article
- Ultrastructure and cardiac impulse propagation: scaling up from microscopic to macroscopic conduction.The Journal of physiology · 2025Review
- New focus on cardiac voltage-gated sodium channel β1 and β1B: Novel targets for treating and understanding arrhythmias?Heart rhythm · 2025Review
- Mitochondrial dysfunction as a central hub linking NaFrontiers in cardiovascular medicine · 2025Review
- The role of ephaptic coupling and gap junctional coupling in modulating the initiation and dynamics of reentrant arrhythmias.PloS one · 2025Article
- Mannitol and hyponatremia regulate cardiac ventricular conduction in the context of sodium channel loss of function.American journal of physiology. Heart and circulatory physiology · 2024Article
- Submillimeter Multifunctional Ferromagnetic Fiber Robots for Navigation, Sensing, and Modulation.Advanced healthcare materials · 2023Article
- Extracellular Perinexal Separation Is a Principal Determinant of Cardiac Conduction.Circulation research · 2023Article
- Multifunctional ferromagnetic fiber robots for navigation, sensing, and treatment in minimally invasive surgery.bioRxiv : the preprint server for biology · 2023Article
- Tmem65 is critical for the structure and function of the intercalated discs in mouse hearts.Nature communications · 2022Article
- Predictive Capability of Metabolic Panels for Postoperative Atrial Fibrillation in Cardiac Surgery Patients.The Journal of surgical research · 2022Article
- Mechanisms of arrhythmia termination during acute myocardial ischemia: Role of ephaptic coupling and complex geometry of border zone.PloS one · 2022Article
- Ephaptic Coupling Is a Mechanism of Conduction Reserve During Reduced Gap Junction Coupling.Frontiers in physiology · 2022Article
- Hypernatremia and intercalated disc edema synergistically exacerbate long-QT syndrome type 3 phenotype.American journal of physiology. Heart and circulatory physiology · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Our laboratory previously demonstrated that perfusate sodium and potassium concentrations can modulate cardiac conduction velocity (CV) consistent with theoretical predictions of ephaptic coupling (EpC). EpC depends on the ionic currents and intercellular separation in sodium channel rich intercalated disk microdomains like the perinexus. We suggested that perinexal width (WP) correlates with changes in extracellular calcium ([Ca(2+)]o). Here, we test the hypothesis that increasing [Ca(2+)]o reduces WP and increases CV. Mathematical models of EpC also predict that reducing WP can reduce sodium driving force and CV by self-attenuation. Therefore, we further hypothesized that reducing WP and extracellular sodium ([Na(+)]o) will reduce CV consistent with ephaptic self-attenuation. Transmission electron microscopy revealed that increasing [Ca(2+)]o (1 to 3.4 mM) significantly decreased WP Optically mapping wild-type (WT) (100% Cx43) mouse hearts demonstrated that increasing [Ca(2+)]o increases transverse CV during normonatremia (147.3 mM), but slows transverse CV during hyponatremia (120 mM). Additionally, CV in heterozygous (∼50% Cx43) hearts was more sensitive to changes in [Ca(2+)]o relative to WT during normonatremia. During hyponatremia, CV slowed in both WT and heterozygous hearts to the same extent. Importantly, neither [Ca(2+)]o nor [Na(+)]o altered Cx43 expression or phosphorylation determined by Western blotting, or gap junctional resistance determined by electrical impedance spectroscopy. Narrowing WP, by increasing [Ca(2+)]o, increases CV consistent with enhanced EpC between myocytes. Interestingly, during hyponatremia, reducing WP slowed CV, consistent with theoretical predictions of ephaptic self-attenuation. This study suggests that serum ion concentrations may be an important determinant of cardiac disease expression.
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