Adenosine triphosphate (ATP)-sensitive potassium channels (K_ATP) which couple cell metabolism to electrical activity are heteromultimers of sulfonylurea receptor (SUR) and inward rectifier K⁺ channel (K_IR6.x) subunits associated with 1∶1 stoichiometry as a tetramer (SUR/ K_IR6.x)₄. SUR and K_IR6.x genes come in pairs in chromosome. K_IR6.x subunit forms the electrical pore of the K_ATP channel and SUR endows the K_ATP channel with sensitivity to regulators such as sulfonylurea drugs, K⁺ channel-opening drugs, and Mg²⁺ nucleotides. The characterizations of K_ATP channel subtypes are determined by the combination of SUR and K_IR6.x subunits. The gates of K_ATP channels are ion-gated by ［ATP］_i and ［ADP］_i. Phosphatidylinositol phosphates (PIPs) antagonized ATP inhibition of K_ATP channels and cellular phosphotransfer cascades also involve in the regulation mechanism of ATP/ADP. K_ATP channels are inhibited by sulfonylurea complexes (SUs) and activated by K⁺ channel-opening drugs. G protein and protein kinase such as PKA, PKC, PKG also participate in the regulation of these channels. K_ATP channels play crucial roles in the secretion of insulin, preconditioning of cardiac myocytes and maintenance of blood vessel tone.