Sarcolemmal Versus Mitochondrial ATP-Sensitive K + Channels and Myocardial Preconditioning

Abstract

Abstract —Ischemic preconditioning (IPC) is a phenomenon in which single or multiple brief periods of ischemia have been shown to protect the heart against a more prolonged ischemic insult, the result of which is a marked reduction in myocardial infarct size, severity of stunning, or incidence of cardiac arrhythmias. Although a number of substances and signaling pathways have been proposed to be involved in mediating the cardioprotective effect of IPC, the overwhelming majority of evidence suggests that the ATP-sensitive potassium channel (K ATP channel) is an important component of this phenomenon and may serve as the end effector in this process. Initially, it was hypothesized that the surface or sarcolemmal K ATP (sarc K ATP ) channel mediated protection observed after IPC; however, subsequent evidence suggested that the recently identified mitochondrial K ATP channel (mito K ATP ) may be the potassium channel mediating IPC-induced cardioprotection. In this review, evidence will be presented supporting a role for either the sarc K ATP or the mito K ATP in IPC and potential mechanisms by which opening these channels may produce cardioprotection; additionally, we will address important questions that still need to be investigated to define the role of the sarc or mito K ATP channel, or both, in cardiac pathophysiology.