Pharmacology of ATP-sensitive potassium channel (K-ATP) openers in models of myocardial ischemia and reperfusion

Recently, much interest has been focused on the pharmacology of ATP-sensitive potassium channels (K-ATP) in myocardial ischemia. K-ATP are thought to be involved with the mechanism of myocardial preconditioning, therefore further increasing the level of interest in these channels. Pharmacologic K-ATP openers have been shown by numerous investigators to protect ischemic-reperfused myocardium. These agents reduce necrosis, improve postischemic functional recovery, and inhibit contracture formation. These protective effects are abolished by K-ATP blockers. The cardioprotective effects of K-ATP openers are independent of vasodilator and cardiodepressant effects, but seem to be mediated by energy conservation (reduced ATP hydrolysis). Action potential shortening is also not correlated with cardioprotection, suggesting a role for intracellular (mitochondrial) K-ATP. Agents have been developed that retain the glyburide-reversible cardioprotective effects of cromakalim but are devoid of vasodilator and action potential shortening activity. Currently, studies are underway to determine the mechanism of cardioprotection. The potential role of mitochondrial K-ATP in the pathogenesis of ischemia is discussed in this review article.