The Interplay of Rogue and Clustered Ryanodine Receptors Regulates Ca(2+) Waves in Cardiac Myocytes

Ca(2+) waves in cardiac myocytes can lead to arrhythmias owing to delayed after-depolarisations. Based on Ca(2+) regulation from the junctional sarcoplasmic reticulum (JSR), a mathematical model was developed to investigate the interplay of clustered and rogue RyRs on Ca(2+) waves. The model successfully reproduces Ca(2+) waves in cardiac myocytes, which are in agreement with experimental results. A new wave propagation mode of “spark-diffusion-quark-spark” is put forward. It is found that rogue RyRs greatly increase the initiation of Ca(2+) sparks, further contribute to the formation and propagation of Ca(2+) waves when the free Ca(2+) concentration in JSR lumen ([Ca(2+)](lumen)) is higher than a threshold value of 0.7 mM. Computational results show an exponential increase in the velocity of Ca(2+) waves with [Ca(2+)](lumen). In addition, more CRUs of rogue RyRs and Ca(2+) release from rogue RyRs result in higher velocity and amplitude of Ca(2+) waves. Distance between CRUs significantly affects the velocity of Ca(2+) waves, but not the amplitude. This work could improve understanding the mechanism of Ca(2+) waves in cardiac myocytes.