Role of intracellular calcium cycling in sinoatrial node myocyte phase-locking

The phase-locking behavior of the sinoatrial node (SAN) may be related to heart rate modulation, which can be physically studied from the perspective of nonlinear dynamics. However, previous studies have treated the myocyte as a pure membrane oscillator without considering its intracellular dynamics. Intracellular calcium cycling (ICC) plays a significant part in pacemaking, but its role in phase-locking is unknown. In the present work, we employ an updated SAN myocyte model incorporating ICC to reinvestigate this problem. The influences of ICC-relevant parameters are determined and explained. Some features which did not appear in older models arise in the presence of ICC. Moreover, we employ our previously proposed theoretical formulas to calculate the phase-locking range. The present work sheds light on the impact of sub-cellular-scale dynamics on the classical SAN phase-locking problem and provides some suggestions for regulating the pacemaking activity.