ATP-sensitive K⁺ (K_ATP) channels are inhibited by intracellular ATP (ATP_i) 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. These channels are clearly heterogeneous. The cardiac K_ATP channel is the prototype of K_ATP channels possessing ∼80 pS of single-channel conductance in the presence of ∼150 mM extracellular K⁺ and opens spontaneously in the absence of ATP_i. A vascular K_ATP channel called a nucleoside diphosphate-dependent K⁺ (K_NDP) channel exhibits properties significantly different from those of the cardiac K_ATP channel. The K_NDP channel has the single-channel conductance of ∼30–40 pS in the presence of ∼150 mM extracellular K⁺, is closed in the absence of ATP_i, and requires intracellular nucleoside di- or triphosphates, including ATP_i to open. Nevertheless, K_ATP and K_NDP channels are both activated by K⁺ channel openers, including pinacidil and nicorandil, and inhibited by sulfonylurea derivatives such as glibenclamide. It recently was found that the cardiac K_ATP channel is composed of a sulfonylurea receptor (SUR)2A and a two-transmembrane-type K⁺ channel subunit Kir6.2, while the vascular K_NDP channel may be the complex of SUR2B and Kir6.1. By precisely comparing the functional properties of the SUR2A/Kir6.2 and the SUR2B/Kir6.1 channels, we shall show that the single-channel characteristics and pharmacological properties of SUR/Kir6.0 channels are determined by Kir and SUR subunits. respectively, while responses to intracellular nucleotides are determined by both SUR and Kir subunits.