Sarcoplasmic reticulum luminal Ca2+ regulates the spontaneous Ca2+ release events and consequently arrhythmia

摘要

The role that sarcoplasmic reticulum (SR) luminal Ca2+ concentration plays in regulating ryanodine receptors (RyRs) is considered to be very important in process of cardiac excitation-contraction coupling. Here we developed a multi-scale mathematical model by coupling a two-dimensional spatio-temporal Ca2+ reaction-diffusion model with an action potential model of the ventricular myocyte. The simulation results showed that 1) the frequency of spontaneous sparks increased when SR Ca2+ content was elevated; 2) when SR Ca2+ was overloaded, spontaneous Ca2+ waves might occur without any external stimulus, and 3) once formed, the propagation of Ca2+ waves was accelerated as the SR Ca2+ content increased. Moreover, those spontaneously occurred Ca2+ release events elevated cytoplasmic [Ca2+]i and then activated inward currents which might cause a delayed afterdepolarization (DAD).