Myocardial infarction resulting from coronary atherosclerosis is the leading cause of death in modern society.Reperfusion is an essential treatment to salvage ischemia myocardium from necrosis, while it also leads to additional damage.Therefore, exploring effective medicines to protect the heart from postischemic injury is one of the major objectives of cardiovascular research.Berbamine is a nature compound of bisbenzylisochinoline alkaloids from Barberry.We found that it displays positive inotropic and lusitropic effects at lower concentrations by increasing myofilament Ca2+ sensitivity via a PKCedependent signaling pathway.Moreover, berbamine preconditioning confers cardioprotection against ischemia/reperfnsion (I/R) injury by attenuating the Ca2+ overloading and preventing the calpain activation through the activating of PI3KAktGSK3 β pathway and subsequently opening of the mitoKATP channel.Furthermore, we demonstrate that berbamine postconditioning conferred the cardioprotective effect against I/R injury by the regulation of autophagy.These findings reveal new roles and mechanisms of berbamine in the heart and cardioprotection against I/R injury.