Function, Regulation, Pharmacology, and Molecular Structure of ATP-Sensitive K+ Channels in the Cardiovascular System

ABSTRACT

K_ATP Channels in Cardiovascular System. ATP-sensitive K⁺ (K_ATP) channels are inhibited by intracellular ATP and activated by intracellular nucleoside diphosphates, and thus provide a link between cellular metabolism and excitability. K_ATP channels are widely distributed in various tissues and may be associated with diverse cellular functions. In the heart, the K_ATP channel appears to be activated during ischemic or hypoxic conditions and may be responsible for the increase of K⁺ efflux and shortening of the action potential duration. Therefore, opening of this channel may result in cardioprotective as well as proarrhythmic effects. In the vascular smooth muscle, the K_ATP channel is believed to mediate the relaxation of vascular tone. Thus, K_ATP channels play important regulatory roles in the cardiovascular system. Furthermore, K_ATP channels are the targets of two important classes of drugs, i.e., the antidiabetic sulfonylureas, which block the channels, and a series of vasorelaxants called "K⁺ channel openers," which tend to maintain the channels in an open conformation. Recently, the molecular structure of K_ATP channels has been clarified. The K_ATP channel in pancreatic β-cells is a complex composed of at least two subunits, a member of inwardly rectifying K⁺ channels and a sulfonylurea receptor. Subsequently, two additional homologs of the sulfonylurea receptor, which form cardiac and smooth muscle type K_ATP channels, respectively, have been reported. Further works are now in progress to understand the molecular mechanisms of K_ATP channel function.