Role of ionic electrodiffusion and ephaptic coupling in cardiac dynamics.

Cardiac myocytes coordinate the heart contractions through electrical signaling, facilitated by gap junctions (GJs) in the intercalated disk. GJs provide low-resistance pathways for electrical propagation between myocytes, acting as the main mechanism for electrical communication in the heart. However, studies show that conduction can persist in the absence of GJs. For instance, GJ knockout mice still display slow and discontinuous electrical propagation, suggesting the presence of alternative communication mechanisms. Ephaptic coupling (EpC) serves as an alternative way for cell communication, relying on electrical fields within narrow clefts between neighboring myocytes. Studies show that EpC can enhance conduction velocity and reduce conduction block, especially when GJs are compromised. Reduced GJs and significant electrochemical gradients are prevalent in various heart diseases. However, existing models often fail to capture their combined influence on cardiac conduction, which limits our understanding of both the physiological and pathological aspects of the heart. Our study aims to address this gap through the development of a two-dimensional discrete multidomain electrodiffusion model that includes EpC. In particular, we investigated the interplay between EpC and multidomain electrodiffusion on action potential (AP) propagation, morphology, and electrochemical properties. Our findings indicate that under strong EpC, Na