Effects of rogue ryanodine receptors on Ca²⁺ sparks in cardiac myocytes

Ca²⁺ sparks and Ca²⁺ quarks, arising from clustered and rogue ryanodine receptors (RyRs), are significant Ca²⁺ release events from the junctional sarcoplasmic reticulum (JSR). Based on the anomalous subdiffusion of Ca²⁺ in the cytoplasm, a mathematical model was developed to investigate the effects of rogue RyRs on Ca²⁺ sparks in cardiac myocytes. Ca²⁺ 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 Ca²⁺ release units (CRUs) of clustered RyRs are regulated by free Ca²⁺ concentration in the JSR lumen (i.e. [Ca²⁺]_lumen). The frequency of spontaneous Ca²⁺ sparks is remarkably increased by the rogue RyRs opening at high [Ca²⁺]_lumen, but not at low [Ca²⁺]_lumen. Hence, the opening of rogue RyRs contributes to the formation of Ca²⁺ sparks at high [Ca²⁺]_lumen. The interplay of Ca²⁺ sparks and Ca²⁺ quarks has been discussed in detail. This work is of significance to provide insight into understanding Ca²⁺ release mechanisms in cardiac myocytes.