Abstract
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.
Highlights
The sinoatrial node (SAN) is the major pacemaker of the heart; its rhythm basically determines the heart rate
Some important studies are as follows: (i) The roles of various sarcolemmal ionic currents in pacemaking activity were investigated by bifurcation analyses.[6,7,8,9] (ii) The entrainment behaviors of self-oscillatory cardiac cells were studied in detail using nonlinear dynamics.[10,11,12,13] (iii) The annihilation of sinus rhythm was explored by analyzing the basin of attraction and the dynamics within.[14–16]
We suggest more physiological experiments in the future to establish the relationship between the N:N pattern and Intracellular calcium cycling (ICC)
Summary
The sinoatrial node (SAN) is the major pacemaker of the heart; its rhythm basically determines the heart rate. Details of the SAN phase-resetting property were explicitly revealed by numerous in vitro and in silico experiments.[23,24,33–36] Some practical problems such as synchronous firing,[37] pacemaker shift,[38] and frequency modulation by acetylcholine[39] were studied . Recent research has shown that the rhythm of the SAN results from an interplay between intracellular calcium cycling (ICC) and transmembrane voltage oscillation. This interplay, referred to as “calcium clock” and “membrane clock” coupling,[4,5,43,44] confers robustness and flexibility on the pacemaking activity. The results for a single cell pave the way to understanding the properties of tissues and organs and may be helpful for understanding and controlling sinus rhythmicity in the future
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