Mechanisms of rectified gap junctional coupling enhancing pacemaking activity of biologically engineered pacemaker cells

Bio-pacemakers offer a potential alternative to electronic devices, yet their stable implementation at cellular and tissue levels remains unresolved. In this computational study, we aimed to investigate possible effects of the electrotonic interaction between cardiac cells and the spatial distribution of the bio-pacemaker on the initiation and conduction of cardiac pacemaking action potentials to surrounding quiescent cardiac tissues. Simulation results demonstrated that (i) a combination of weak gap junctional electrical coupling among PMs; and (ii) rectified coupling arising from heterotypic gap junction expressions between the PM and ventricle yielded the best stable and robust bio-pacemaker for pacing and driving surrounding ventricular tissue. Furthermore, Isolated or septal placement improved ventricular pacing efficacy. This study adopts a digital health approach, providing an important theoretical foundation for the simulation of new clinical therapies.