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Ephaptic Coupling Is a Mechanism of Conduction Reserve During Reduced Gap Junction Coupling
Joyce Lin1, Anand Abraham2,3, Sharon A George3,4
1Department of Mathematics, California Polytechnic State University, San Luis Obispo, CA, United States.
Frontiers in Physiology
|May 23, 2022
Summary
Reduced gap junction (GJ) coupling in heart disease is complex. Conduction reserve relies more on ephaptic coupling (EpC) than charge accumulation, especially with narrowed cell gaps, maintaining cardiac electrical activity.
Area of Science:
- Cardiovascular Physiology
- Biophysics
- Cardiac Electrophysiology
Background:
- Cardiac pathologies often involve reduced gap junction (GJ) coupling, impacting cardiac conduction velocity (CV).
- The relationship between GJ protein expression and cardiac function is debated, with concepts like conduction reserve complicating direct correlations.
- Ephaptic coupling (EpC) and intracellular charge accumulation are proposed mechanisms maintaining CV despite low GJ coupling.
Purpose of the Study:
- To investigate the interplay between ephaptic coupling (EpC) and intracellular charge accumulation in the context of GJ remodeling.
- To elucidate the relative contributions of EpC and charge accumulation to cardiac action potential parameters and conduction velocity during pathological conditions.
Main Methods:
- Multicellular computational simulations of myocardial cell conduction under varied GJ coupling and intercellular distances.
- Perfused mouse heart experiments using wild-type and Gja1 heterozygous null mice, mimicking simulated conditions.
- Analysis of action potential upstroke velocity (dV/dt_max) and conduction velocity in relation to GJ coupling, perinexal width (Wp), and sodium channel distribution.
Main Results:
- Both simulations and experiments demonstrated that reduced GJ coupling decreases, while narrowed perinexal width (Wp) increases, the action potential upstroke rate.
- These effects are pronounced when sodium channels are densely expressed at myocyte ends.
- Conduction reserve appears to be more significantly influenced by EpC than by intracellular charge accumulation.
Conclusions:
- Cardiac conduction reserve during GJ uncoupling is predominantly mediated by ephaptic coupling, not intracellular charge accumulation.
- Narrowing of the intercalated disc space (Wp) enhances the contribution of EpC to maintaining cardiac electrical propagation.
- Understanding these mechanisms is crucial for addressing cardiac arrhythmias associated with GJ remodeling.
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