Abstract
The sarcoplasmic reticulum (SR) primarily serves as the intracellular Ca(2+) store in cardiac myocytes, mediating cellular function under cardiac physiology and diseases. However, the properties of cardiac SR Ca(2+) have not yet been fully determined, particularly in rats and mice, which are the most commonly used experimental species in studies on cardiac physiology and diseases. Here, we developed a spatially detailed numerical model to deduce Ca(2+) movements inside the junctional SR (jSR) cisternae of rat cardiomyocytes. Our model accurately reproduced the jSR Ca(2+) kinetics of local and global SR Ca(2+) releases reported in a recent experimental study. With this model, we revealed that jSR Ca(2+) kinetics was mostly determined by the total release flux via type 2 ryanodine receptor (RyR2) channels but not by RyR2 positioning. Although Ca(2+) diffusion in global SR was previously reported to be slow, our simulation demonstrated that Ca(2+) diffused very quickly inside local jSR cisternae and the decrease in the diffusion coefficient resulted in a significant reduction of jSR Ca(2+) depletion amplitude. Intracellular Ca(2+) was typically experimentally detected with fluorescence dye. Our simulation revealed that when the dynamical characteristics of fluorescence dye exerted a minimal effect on actual Ca(2+) mobility inside jSR, the reaction rate of the dye with Ca(2+) could significantly affect apparent jSR Ca(2+) kinetics. Therefore, loading a chemical fluorescence dye with fast kinetics, such as Fluo-5N, into SR is important for Ca(2+) measurement inside SR. Overall, our model provides new insights into deciphering Ca(2+) handling inside nanoscopic jSR cisternae in rat cardiomyocytes.