AUTHOR=Chen Xudong , Feng Yundi , Huo Yunlong , Tan Wenchang TITLE=The Interplay of Rogue and Clustered Ryanodine Receptors Regulates Ca2+ Waves in Cardiac Myocytes JOURNAL=Frontiers in Physiology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00393 DOI=10.3389/fphys.2018.00393 ISSN=1664-042X ABSTRACT=

Ca²⁺ waves in cardiac myocytes can lead to arrhythmias owing to delayed after-depolarisations. Based on Ca²⁺ regulation from the junctional sarcoplasmic reticulum (JSR), a mathematical model was developed to investigate the interplay of clustered and rogue RyRs on Ca²⁺ waves. The model successfully reproduces Ca²⁺ 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 Ca²⁺ sparks, further contribute to the formation and propagation of Ca²⁺ waves when the free Ca²⁺ concentration in JSR lumen ([Ca²⁺]_lumen) is higher than a threshold value of 0.7 mM. Computational results show an exponential increase in the velocity of Ca²⁺ waves with [Ca²⁺]_lumen. In addition, more CRUs of rogue RyRs and Ca²⁺ release from rogue RyRs result in higher velocity and amplitude of Ca²⁺ waves. Distance between CRUs significantly affects the velocity of Ca²⁺ waves, but not the amplitude. This work could improve understanding the mechanism of Ca²⁺ waves in cardiac myocytes.