Speaker
Description
Cardiac action potential (AP) propagation occurs through gap junction (GJ)-rich intercalated discs (IDs). However, recent experimental studies show that GJ knockout mice can still maintain heart structure and function, even when GJs are undetectable at IDs. Ephaptic coupling (EpC), an electric field effect across the narrow, tortuous IDs, provides an alternative mechanism for cell-to-cell communication when GJs are impaired. Given the current lack of direct experimental evidence for EpC, modeling studies are essential for understanding its physiological and pathological roles in the heart.
Our research investigates how EpC and ionic electrodiffusion influence arrhythmogenesis in the hearts. We developed the first two-dimensional multidomain electrodiffusion model incorporating EpC. Our findings demonstrate that strong EpC suppresses the initiation of reentry, resulting in absent or nonsustained reentrant activity with a reduced maximum dominant frequency (DF), although it can also introduce transient instability and heterogeneity in cardiac dynamics. In contrast, weak EpC supports the initiation of sustained reentry, characterized by a stable rotor and high DF. Strong EpC terminates reentry through self-attenuation, while moderate EpC does so through self-collision. Additionally, we applied spectrum theory to analyze the impact of EpC on one-dimensional wave trains. Our results show that EpC reduces both the frequency and amplitude of wave trains.
Bibliography
@article{wei2025mechanisms,
title={Mechanisms of reentry arrhythmia termination with ephaptic coupling and gap junctional coupling},
author={Wei, Ning and Lin, Joyce},
journal={Journal of Theoretical Biology},
pages={112308},
year={2025},
publisher={Elsevier}
}
@article{wei2025analytical,
title={Analytical Insights into Ephaptic Coupling and Its Effect on Conduction Velocity},
author={Wei, Ning and Mori, Yoichiro},
journal={Journal of Mathematical Biology},
volume={91},
number={6},
pages={85},
year={2025},
publisher={Springer}
}
@article{wei2025role,
title={Role of ionic electrodiffusion and ephaptic coupling in cardiac dynamics},
author={Wei, Ning and Mori, Yoichiro},
journal={Biophysical Journal},
volume={124},
number={18},
pages={3060--3074},
year={2025},
publisher={Elsevier}
}
@article{wei2022mechanisms,
title={Mechanisms of arrhythmia termination during acute myocardial ischemia: Role of ephaptic coupling and complex geometry of border zone},
author={Wei, Ning and Tolkacheva, Elena G},
journal={PloS one},
volume={17},
number={3},
pages={e0264570},
year={2022},
publisher={Public Library of Science San Francisco, CA USA}
}
@article{wei2025roleb,
title={The role of ephaptic coupling and gap junctional coupling in modulating the initiation and dynamics of reentrant arrhythmias},
author={Wei, Ning and Tolkacheva, Elena G},
journal={PloS one},
volume={20},
number={8},
pages={e0330016},
year={2025},
publisher={Public Library of Science San Francisco, CA USA}
}
