Sarcoplasmic reticulum calcium leak and heart failure

Calcium ions play a key role in maintaining the equilibrium of excitation-contraction coupling process in the heart. The increased calcium concentration is primarily responsible for the whole cell activation, relevant signaling pathways involved in regulation of sarcomeric gene expression, and have broader effects on cardiac functioning. Sarcoplasmic reticulum, playing an important role in maintaining the intracellular calcium homeostasis, is the critical factor involved in excitation-contraction coupling in cardiomyocytes. The increased activity of ryanodine receptor 2 (RyR2) channel in diastolic phase leads to its abnormal opening and/or incomplete closing, inducing significant calcium leak from sarcoplasmic reticulum. More and more evidences indicate that, abrupt increase in local calcium concentration, especially in end-stage heart failure, leads to sarcoplasmic reticulum abnormalities as well as reorganization of cardiac structure and its function. Here, we primarily emphasized on the mechanism responsible for calcium leak and explored its therapeutic option, if any, to prevent the development and progression of heart failure by regulating the increased calcium concentration locally.