Premium
Mitochondrial K ATP channels and cardioprotection
Author(s) -
Patel Hemal H.,
Gross Garrett J.
Publication year - 2002
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10037
Subject(s) - cardioprotection , ischemic preconditioning , potassium channel , cardiology , medicine , ischemia , atp sensitive potassium channel , membrane potential , myocardial infarction , coronary occlusion , myocyte , myocardial stunning , pharmacology , anesthesia , chemistry , endocrinology , biochemistry , glibenclamide , diabetes mellitus
Since its identification in 1983, the myocardial ATP‐sensitive potassium channel (K ATP channel) has been recognized as an important ion channel that couples the cellular energy status to electrical activity in ischemic or hypoxic myocytes, and early studies with selective potassium channel openers suggested that opening this channel may result in cellular protection. This concept was strengthened in 1992, when it was shown that this channel was an integral part of ischemic preconditioning (IPC), a phenomenon in which one or several short periods of coronary artery occlusion were shown to protect the heart from a more prolonged coronary artery occlusion. Endpoints of injury, which have been used as indices to demonstrate the efficacy of IPC, include a reduction in myocardial infarct size, a reduction in contractile dysfunction after brief periods of ischemia (myocardial stunning), and a decrease in the incidence of cardiac arrhythmias during coronary artery occlusion and/or reperfusion. Since the seminal observation of a myocrdial K ATP channel, two K ATP channels have been identified: one in the sarcolemmal membrane (sarc K ATP ) and one in the inner mitochondrial membrane (mito K ATP ). There is evidence to support a role for both channels in mediating cardioprotection; however, the majority of recent evidence suggests that the mito K ATP channel is the major channel responsible for cardioprotection after IPC or the administration of K ATP opener drugs. This review will summarize the evidence supporting a role for the mito K ATP channel in both acute and delayed preconditioning produced by ischemia. The review will also summarize, from a pharmacological viewpoint, the potential mechanisms responsible for the cardioprotection observed and the potential clinical implications of developing drugs that are selective mito K ATP channel openers. Drug Dev. Res. 55:17–21, 2002. © 2002 Wiley‐Liss, Inc.