Qualitative Support for the Gradient Model of Cardiac Pacemaker Heterogeneity

In this study, we investigate the role of sinoatrial node (SAN) cellular heterogeneity in normal cardiac pacemaker function. Using detailed ionic models of electrical activity in SAN and atrial myocytes, we have formulated a number of models of SAN heterogeneity based on discrete-region (in which central and peripheral SAN type cell are separated into discrete regions), gradient and mosaic models of SAN organisation. Simulations of each of the different models were performed in one and two dimensions in the presence of both uniform and linearly increasing conductivity profiles. Simulation results suggest that the gradient model, in which cells display a smooth variation in membrane properties from the center to the periphery of the SAN, best reproduces action potential waveshapes and a site of earliest activation consistent with experimental observations in the intact SAN. We therefore propose that the gradient model of SAN heterogeneity represents the most plausible model of SAN organisation