Mechanisms by which K_ATP channel openers produce acute and delayed cardioprotection

Mitochondria are being increasingly studied for their critical role in cell survival. Multiple diverse signaling pathways have been shown to converge on the K⁺-sensitive ATP channels as the effectors of cytoprotection against necrosis and apoptosis. The role of potassium channel openers in regulation and transformation of cell membrane excitability, action potential and electrolyte transfer has been extensively studied. Cardiac mitoK _ATP channels are the key effectors in cardioprotection during ischemic preconditioning, as yet with an undefined mechanism. They have been hypothesized to couple myocardial metabolism with membrane electrical activity and provide an excellent target for drug therapy. A number of K_ATP channel openers have been characterized for their beneficial effects on the myocardium against ischemic injury. This review updates recent progress in understanding the physiological role of K_ATP channels in cardiac protection induced by preconditioning and highlights relevant questions and controversies in the light of published data.