The Effects of Quarky Ca2+ Release on Ca2+ Spark in Cardiac Myocytes

Abstract

Ca2+ sparks and quarks are significant events of Ca2+ releasing from the sarcoplasmic reticulum (SR) in cardiac myocytes, but caused by different releasing mechanisms. The objective of the study is to investigate the effects of Ca2+ quarks on the incidence and properties of Ca2+ sparks theoretically and experimentally. A two‐dimensional (2D) model was developed to simulate Ca2+ sparks and quarks based on the anomalous subdiffusion of Ca2+ in the cytoplasm. The numerical model included some specific features of Ca2+ quarks, such as long duration and small currents. The model was validated against the experimental measurements. It was found that Ca2+ sparks and quarks coexisted at a single release site. Quarky Ca2+ release (QCR) events from rogue ryanodine receptors (RyRs) can activate the clustered RyRs and hence result in Ca2+ sparks with different quantal units. Moreover, the sensitivity analysis showed some variables of rogue RyRs that may exist under pathological conditions significantly affected the incidence of Ca2+ sparks. This study provided some novel insights into the mechanisms of SR Ca2+ releasing events in cardiac myocytes.Support or Funding InformationThis work was supported by the National Natural Science Foundation of China (Grant No. 11272014 and No. 11328201) and the National Key Basic Research Program of China (Grant No. 2013CB531200).