Gap junctional and ephaptic coupling in cardiac electrical propagation: homocellular and heterocellular perspectives

Electrical communication in the heart is crucial for maintaining normal cardiac function. Traditionally, gap junctional coupling between cardiomyocytes has been accepted as the primary mechanism governing electrical propagation in the heart. However, numerous studies have demonstrated that gap junctions are also present between different cell types in heterocellular structures and disruption of such gap junctional coupling can be associated with cardiac dysfunction. In addition to gap junctional coupling, ephaptic coupling has been proposed as another mechanism for electrical communication between cardiomyocytes. Reducing ephaptic coupling has been shown to have negative impacts on cardiac conduction. While the existence of ephaptic coupling between different types of cardiac cell is under investigation, a recent study suggests that ephaptic coupling at heterocellular contacts between cardiomyocytes and fibroblasts may provide a proarrhythmic substrate in cardiac disease. In this review, we examine the current literature on electrical communication in the heart, including gap junctional and ephaptic coupling in homocellular and heterocellular contexts. Further, we offer a perspective on gaps in knowledge and opportunities for further advancing our understanding of electrical coupling mechanisms in action potential propagation in the heart.