Cardiac KATP channels and ischemic preconditioning: current perspectives.
Ischemic preconditioning (IPC) is a naturally occurring protective mechanism in the heart and is triggered by brief ischemic insults preceding a sustained ischemic period. The artificial induction of the protective effects of IPC are potentially of great benefit to postinfarct patients and would serve to augment traditional surgical and thrombolytic treatment regimens. As yet, no agent has been developed to trigger IPC specifically. The mechanisms underlying IPC have been the focus of intense study, and many components of the IPC framework have been elucidated. Adenosine, noradrenalin, angiotensin II and endothelin are several of the key inducers of IPC. Signal transduction events downstream of receptor activation converging on protein kinase C stimulation are thought to trigger the intracellular pathways leading to 'preconditioning'. Although the complete sequence of events beneath IPC are not clear, several of the end effectors for the initiation of IPC are. For instance, activation of a class of potassium channels that are sensitive to internal ATP (KATP channels) can induce IPC and may be at least one of the targets for the action of protein kinase C. The precise mechanisms by which stimulation of KATP channels protects the myocardium are still under debate and are discussed in this review. It seems likely that both the plasma membrane and mitochondrial KATP channel populations are involved in IPC. Because KATP channels are rich and varied pharmacologically, it may be possible to target therapeutic agents at the cardiac channel isoform. Such compounds would likely meet the pharmacological criteria for a 'conditioning' agent.
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University of Calgary, Calgary, Canada. plight@acs.ucalgary.ca
D000255:Adenosine Triphosphate / Q000378:metabolism*; D005260:Female; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology
D018377:Neurotransmitter Agents; D000255:Adenosine Triphosphate