Effects of rogue ryanodine receptors on ca2+ sparks in cardiac myocytes

Abstract

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.