Spatial and functional heterogeneity among pacemaker cell populations increases robustness and flexibility of SA node tissue pacemaker function in silico

Abstract

Each heartbeat is initiated by pacemaker cells operating within the sinoatrial node (SAN). While SAN cells exhibit substantial spatial heterogeneity of their electrophysiological and Ca cycling parameters, the impact of this heterogeneity on SAN function has not been established. We investigated this problem numerically in a SAN tissue model computed by a GPU (25x25 cell grid), with each cell described by a coupled-clock Maltsev-Lakatta model. Action potential (AP) generation was examined in scenarios representing different cell populations with different degrees of spatial and functional heterogeneity of the key coupled-clock functional parameters: maximal L-type Ca current conductance (gCaL) and sarcoplasmic reticulum Ca pumping rate (Pup).