Sarcoplasmic Reticulum Luminal [Ca

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).