Function, regulation, pharmacology, and molecular structure of ATP-sensitive K+ channels in the 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 beta-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.