Modulation of sarcoplasmic reticulum function: a new strategy in cardioprotection?

This article reviews the experimental evidence suggesting that cytosolic Ca(2+) overload plays a major role in the development of myocardial injury during ischemia-reperfusion and that Ca(2+) release from the sarcoplasmic reticulum (SR) is of crucial importance in the early phase of ischemia. It is suggested that interventions able to deplete the SR Ca(2+) pool and/or to reduce the rate of SR Ca(2+) release should be cardioprotective. This thesis is supported by the review of experimental studies in which modulators of the SR Ca(2+)-ATPase or SR Ca(2+) release channel (ryanodine receptor) have been used. In addition, the role of the SR in ischemic preconditioning and in some instances of toxic myocardial injury (particularly, anthraquinone-induced injury) is discussed.