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

The role that sarcoplasmic reticulum (SR) luminal Ca
²⁺
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 Ca
²⁺
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 Ca
²⁺
content was elevated; 2) when SR Ca
²⁺
was overloaded, spontaneous Ca
²⁺
waves might occur without any external stimulus, and 3) once formed, the propagation of Ca
²⁺
waves was accelerated as the SR Ca
²⁺
content increased. Moreover, those spontaneously occurred Ca
²⁺
release events elevated cytoplasmic [Ca
²⁺
]i and then activated inward currents which might cause a delayed afterdepolarization (DAD).