Effects of rogue ryanodine receptors on Ca(2+) sparks in cardiac myocytes

Ca(2+) sparks and Ca(2+) quarks, arising from clustered and rogue ryanodine receptors (RyRs), are significant Ca(2+) release events from the junctional sarcoplasmic reticulum (JSR). Based on the anomalous subdiffusion of Ca(2+) in the cytoplasm, a mathematical model was developed to investigate the effects of rogue RyRs on Ca(2+) sparks in cardiac myocytes. Ca(2+) quarks and sparks from the stochastic opening of rogue and clustered RyRs are numerically reproduced and agree with experimental measurements. It is found that the stochastic opening Ca(2+) release units (CRUs) of clustered RyRs are regulated by free Ca(2+) concentration in the JSR lumen (i.e. [Ca(2+)](lumen)). The frequency of spontaneous Ca(2+) sparks is remarkably increased by the rogue RyRs opening at high [Ca(2+)](lumen), but not at low [Ca(2+)](lumen). Hence, the opening of rogue RyRs contributes to the formation of Ca(2+) sparks at high [Ca(2+)](lumen). The interplay of Ca(2+) sparks and Ca(2+) quarks has been discussed in detail. This work is of significance to provide insight into understanding Ca(2+) release mechanisms in cardiac myocytes.