Type 2 ryanodine receptor: A novel therapeutic target in myocardial ischemia/reperfusion

Cardiac pathologies remain the main cause of mortality worldwide. Among them the most common cause is cardiac ischemia. The rapid reperfusion after coronary occlusion has considerably improved the cardiac outcome, however reperfusion per se has deleterious effect also called reperfusion injuries. Cytosolic calcium overload is now well admitted as an essential pathophysiological mechanism involved in reperfusion injuries although the source and origin of calcium remain to be determined. Recent works have pointed out the potential defect of sarcoplasmic reticulum calcium release channels (ryanodine receptor, RyR) as a primary cause of calcium overload during ischemia-reperfusion. This finding opens new pharmacological perspectives in limiting reperfusion injuries since allosteric modulators able to restore and prevents RyR dysfunction have been developed during the last decade. (C) 2013 Elsevier Inc. All rights reserved.