Wei Ning, Tolkacheva Elena G
Department of Mathematics, Purdue University, 150 N. University St, West Lafayette, Indiana, United States of America.
Department of Biomedical Engineering, University of Minnesota, 312 Church St SE, Minneapolis, Minnesota, United States of America.
PLoS One. 2025 Aug 19;20(8):e0330016. doi: 10.1371/journal.pone.0330016. eCollection 2025.
Cardiac myocytes synchronize through electrical signaling to contract heart muscles, facilitated by gap junctions (GJs) located in the intercalated disc (ID). GJs provide low-resistance pathways for electrical impulse propagation between myocytes, considered the primary mechanism for electrical communication in the heart. However, research indicates that conduction can persist without GJs. Ephaptic coupling (EpC), which depends on electrical fields in the narrow ID between adjacent myocytes, offers an alternative mechanism for cardiac conduction when GJs are impaired. Research suggests that EpC can enhance conduction velocity (CV) and reduce the likelihood of conduction block (CB), particularly when GJs are impaired, demonstrating the anti-arrhythmic potential of EpC. Reduced GJ communication increases the susceptibility of heart to arrhythmias due to ectopic or triggered activity, highlighting the pro-arrhythmic effect of GJ uncoupling. However, the interplay between GJs and EpC, and their roles in the initiation, dynamics, and termination of arrhythmias, remain unclear. Reentry, characterized by a loop of electrical activity, is a common mechanism underlying arrhythmogenesis in the heart. This study aims to explore the interplay between EpC and GJs on reentry initiation and its underlying dynamics. Specifically, we employed a two-dimensional (2D) discrete bidomain model that integrates EpC to simulate ephaptic conduction during reentry. We quantitatively assessed the outcomes of reentry initiation and the resulting dynamics across different levels of EpC, GJs, and initial perturbations. The results show that sufficiently strong EpC (i.e., sufficiently narrow clefts) tends to suppress reentry initiation, resulting in absent or non-sustained reentrant activity, while also introducing transient instability and heterogeneity into the cardiac dynamics. In contrast, relatively weak EpC (wide clefts) support sustained reentry with a stable rotor. Furthermore, we found that sufficiently strong EpC can lower the maximal dominant frequency observed during reentrant activity. Overall, this suggests that strong EpC exerts an anti-arrhythmic effect.
心肌细胞通过电信号同步收缩心肌，这一过程由位于闰盘（ID）中的缝隙连接（GJ）促进。GJ为心肌细胞之间的电冲动传播提供低电阻通路，被认为是心脏电传导的主要机制。然而，研究表明，即使没有GJ，传导仍可继续。ephaptic耦合（EpC）依赖于相邻心肌细胞之间狭窄ID中的电场，当GJ受损时为心脏传导提供了另一种机制。研究表明，EpC可以提高传导速度（CV）并降低传导阻滞（CB）的可能性，特别是当GJ受损时，这表明EpC具有抗心律失常的潜力。GJ通讯减少会增加心脏因异位或触发活动而发生心律失常的易感性，突出了GJ解偶联的促心律失常作用。然而，GJ和EpC之间的相互作用及其在心律失常的起始、动态变化和终止中的作用仍不清楚。折返以电活动环路为特征，是心脏心律失常发生的常见机制。本研究旨在探讨EpC和GJ在折返起始及其潜在动力学方面的相互作用。具体而言，我们采用了一个二维（2D）离散双域模型，该模型整合了EpC来模拟折返期间的ephaptic传导。我们定量评估了折返起始的结果以及在不同EpC、GJ和初始扰动水平下产生的动力学。结果表明，足够强的EpC（即足够窄的间隙）倾向于抑制折返起始，导致无折返活动或折返活动不持续，同时也会给心脏动力学引入短暂的不稳定性和异质性。相比之下，相对较弱的EpC（宽间隙）支持稳定转子的持续折返。此外，我们发现足够强的EpC可以降低折返活动期间观察到的最大主导频率。总体而言，这表明强EpC具有抗心律失常作用。
