Modulation of Cardiac Pacemaker Inter Beat Intervals by Sinoatrial Fibroblasts – A Numerical Study

Abstract

The potential effect of sinoatrial fibroblasts on beat rate and variability of the cardiac pacemakers is not yet fully understood. Heterocellular coupling formation and fibroblast proliferation during diseased conditions may further signify the impact of those cells on sinoatrial node function. In this study we numerically modeled the impact of varying numbers of fibroblasts that are electrically coupled to a single pacemaker cell on several electrophysiological parameters. We employed cellular kinetics of the rabbit sinoatrial myocyte, and employed a range of potential gap junctional coupling between fibroblasts and myocytes. We show that increasing numbers of attached and coupled fibroblasts result in depolarization of the resting membrane potential of the pacemaker cell, as well as in attenuation in its action potential magnitude. We also demonstrate that the mean pacemaker inter-beat interval (IBI) was modulated in a non-linear, bi-phasic way by increasing numbers of attached fibroblasts, whereby an initial phase of decreasing IBIs was followed by a significant phase of exponentially increasing IBIs. These observations were more substantial for increased gap junctional coupling between the two cell types. We finally show that IBI variability exponentially increased with increasing numbers of attached and electrically coupled fibroblasts. Again, this effect was stronger with higher values of gap junctional coupling. We postulate that the last observation is related to the role of fibroblasts in amplifying membrane voltage fluctuations of attached myocytes.