A comparison of 1-D models of cardiac pacemaker heterogeneity.

In this paper, we investigate the role of sinoatrial node (SAN) cellular heterogeneity in two key aspects of normal cardiac pacemaker function: frequency entrainment of the SAN, and propagation of excitation into the atrial tissue. Using detailed ionic models of electrical activity in SAN and atrial myocytes, we have formulated a number of one-dimensional 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 organization. Each of the different models were assessed on their ability to achieve frequency entrainment of the SAN and activation of the adjoining atrial tissue in the presence of both uniform and linearly increasing conductivity profiles. Simulation results suggest that the gradient model of SAN heterogeneity, in which cells display a smooth variation in membrane properties from the center to the periphery of the SAN, produces action potential waveshapes and a site of earliest activation consistent with experimental observations in the intact SAN. The gradient model also achieves frequency entrainment of the SAN more easily than other models of SAN heterogeneity. Based on these results, we conclude that the gradient model of SAN heterogeneity, in the presence of a uniform conductivity profile, is the most likely model of SAN organization.