Sarcolemmal versus mitochondrial ATP-sensitive K+ channels and myocardial preconditioning

Ischemic preconditioning (IPC) is a phenomenon in which single or multiple brief periods of ischemia have been shown to protect the heart against a mo re prolonged ischemic insult, the result of which is a marked reduction in myocardial infarct size, severity of stunning, or incidence of cardiac arrh ythmias. Although a number of substances and signaling pathways have been p roposed to be involved in mediating the cardioprotective effect of IPC, the overwhelming majority of evidence suggests that the ATP-sensitive potassiu m channel (K-ATP channel) is an important component of this phenomenon and may serve as the end effector in this process. Initially, it was hypothesiz ed that the surface or sarcolemmal K-ATP (sarc K-ATP) channel mediated prot ection observed after IPC; however, subsequent evidence suggested that the recently identified mitochondrial K-ATP channel (mito K-ATP) may be the pot assium channel mediating IPC-induced cardioprotection. In this review, evid ence will be presented supporting a role for either the sarc K-ATP or the m ite K-ATP in IPC and potential mechanisms by which opening these channels m ay produce cardioprotection; additionally, we will address important questi ons that still need to be investigated to define the role of the sarc or mi te K-ATP channel, or both, in cardiac pathophysiology.