ATP-Sensitive Potassium Channel Openers and Blockers in the Cardiovascular System: Physiology,Pharmacology,and Clinical Effects

Abstract

Adenosine triphosphate (ATP)-sensitive potassium chan nels (K.ATP channels), a subclass of potassium channels activated by a low intracellular ATP concentration, have been described in various tissue types, including the heart muscle and vascular smooth muscle. In ventricu lar myocytes, activation of these channels is considered protective, because their activation caused by hypoxia or ischemia results in cell energy preservation. Activa tion of K.ATP channels in vascular smooth muscle cells causes hyperpolarization of the cell membrane, muscle cell relaxation, and vasodilation. Potassium channel openers are pharmacologic activators of K.ATP chan nels. Their protective effects on the ischemic myocar dium and their vasodilating properties have been stud ied extensively. Sulfonylurea derivatives, widely used in the treatment of noninsulin-dependent diabetes melli tus, are considered selective blockers of K.ATP channels and have been used in many experiments to show K.ATP channel involvement. This article focuses on these issues and the clinical effects and potentials of K.ATP channel modulation.