A pacemaker cell pair model based on the phase response curve.

Abstract

A pacemaker cell pair model and the dynamic interaction between the two pacemaker cells is described in this paper. It is an extension of our single pacemaker cell model, in which we studied its response to repetitive external depolarization stimulations. This model is a simple model based on the two most important functional properties of the cardiac pacemaker cells: its intrinsic pacemaker cycle length, which is an 'internal' parameter of the cell, and the phase response curve (PRC), which is an 'overall collective' function. The PRC contains all the 'information' about the possible interactions of the pacemaker cell with the outside world (interaction with surrounding cells, external stimulus, etc.). First, we examined the properties and solutions of 1:1 synchronization between two pacemaker cells. We found that in order to achieve synchronization between two pacemaker cells, there should be limitations on the PRC parameters, which depend on the cells intrinsic cycle lengths. Next, we investigated the 2:1 entrainment state between two interacting pacemaker cells. We found that there is not necessarily a unique solution for this state as there was for the 1:1 state. Finally, we ran our computer model to investigate the properties of more complex patterns of entrainment between two pacemaker cells. As a result of our analytical study, we unveil two new important parameters, which are fully defined as a function of the PRC parameters: (1) the 'accelerator factor' which describes the tendency of a pair of interacting pacemaker cells to synchronize at a common cycle length, which is closer to the faster cycle of the pair; (2) the 'degree of coupling', which describes the range of the 1:1 synchronization and the 'strength' of the interaction between a pair of interacting pacemaker cells. Those two interaction parameters arise as helpful 'tools' for the understanding of synchronization and mutual entrainment mechanisms between pacemaker cells. Therefore, this study establishes the PRC as an important determinant and a useful approach for the understanding of the dynamic interaction of pacemaker cells among themselves and with the outside world.