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INVITED REVIEWS

K_ATP channels and myocardial preconditioning: an update

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Ischemic or myocardial preconditioning (IPC) is a phenomenon whereby brief periods of ischemia have been shown to protect the myocardium against a more sustained ischemic insult. The result of IPC may be manifest as a marked reduction in infarct size, myocardial stunning, or incidence of cardiac arrhythmias. Whereas many endogenous neurotransmitters, peptides, and hormones have been proposed to play a role in the signal transduction pathways mediating the cardioprotective effect of IPC, nearly universal evidence indicates the involvement of the ATP-sensitive potassium (K_ATP) channel. Initial evidence suggested that the surface or sarcolemmal K_ATP (sarcK_ATP) channel triggered or mediated the cardioprotective effects of IPC; however, more recent findings have suggested a major role for a mitochondrial site or possibly a mitochondrial K_ATP channel (mitoK_ATP). This review presents evidence that supports a role for these two channels as a trigger and/or downstream mediator in the phenomenon of IPC or pharmacologically induced PC as well as recent evidence that suggests the involvement of a mitochondrial calcium-activated potassium (mitoK_ca) channel or the electron transport chain in mediating the beneficial effects of IPC or pharmacologically induced PC.

ischemia; electron transport chain

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