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.
Highlights
Ca2+ sparks regulate the excitation–contraction coupling in heart muscle [1,2,3], and are activated by the opening of clustered ryanodine receptors (RyRs) on the junctional sarcoplasmic reticulum (JSR) membrane [4,5,6]
The computational domain is a square of 5 × 5 μm2 with the distribution of clustered and rogue RyRs on the JSR membrane in figure 1c
The Ca2+ release events from JSRs agree with experimental measurements in cardiac myocytes
Summary
Ca2+ sparks regulate the excitation–contraction coupling in heart muscle [1,2,3], and are activated by the opening of clustered ryanodine receptors (RyRs) on the junctional sarcoplasmic reticulum (JSR) membrane [4,5,6]. The discovery of quarky Ca2+ releases (QCRs or Ca2+ quarks) due to the opening of rogue RyRs has been shown as a significant Ca2+ release mechanism relevant to ‘invisible Ca2+ leak’ [7,8,9]. Ca2+ sparks and quarks occur spontaneously and concurrently.
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