Models of cardiomyocyte-non-myocyte electrical interactions

Cardiac non-myocytes are increasingly recognized as active contributors to cardiac electrophysiology. Fibroblasts have been shown to form connexin-based electrotonic connections with cardiomyocytes (CM) in situ, and more recently, macrophages have also been found to engage in electrotonic interactions with CM. This growing evidence requires a conceptual reassessment of cardiac electrophysiology. However, studying heterocellular coupling in situ remains challenging. These experimental uncertainties define a scope for computational modelling and simulation. In this review, we provide an overview of computational models of heterocellular coupling across multiple spatial scales, from single-cell interactions to whole-organ dynamics. We start by presenting the rationale for studying cardiac heterocellular coupling that is based on clinical and experimental evidence, followed by an overview of computational modelling studies, and conclude with an outlook to future research directions.