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

KATP Channels in Cardiovascular System. ATP‐sensitive K+ (KATP) channels are inhibited by intracellular ATP and activated by intracellular nucleoside diphosphates, and thus provide a link between cellular metabolism and excitability. KATP channels are widely distributed in various tissues and may be associated with diverse cellular functions. In the heart, the KATP 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 KATP channel is believed to mediate the relaxation of vascular tone. Thus, KATP channels play important regulatory roles in the cardiovascular system. Furthermore, KATP 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 KATP channels has been clarified. The KATP 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 KATP channels, respectively, have been reported. Further works are now in progress to understand the molecular mechanisms of KATP channel function.