Aguilar-Bryan, Lydia, John P. Clement IV, Gabriela Gonzalez, Kumud Kunjilwar, Andrey Babenko, and Joseph Bryan. Toward Understanding the Assembly and Structure of K ATP Channels. Physiol. Rev. 78: 227–245, 1998.—Adenosine 5′-triphosphate-sensitive potassium (K ATP) channels couple metabolic events to membrane electrical activity in a variety of cell types. The cloning and reconstitution of the subunits of these channels demonstrate they are heteromultimers of inwardly rectifying potassium channel subunits (K IR 6. x) and sulfonylurea receptors (SUR), members of the ATP-binding cassette (ABC) superfamily. Recent studies indicate that SUR and K IR 6. x associate with 1: 1 stoichiometry to assemble a large tetrameric channel,(SUR/K IR 6. x) 4. The K IR 6. x subunits form the channel pore, whereas SUR is required for activation and regulation. Two K IR 6. x genes and two SUR genes have been identified, and combinations of subunits give rise to K ATP channel subtypes found in pancreatic β-cells, neurons, and cardiac, skeletal, and smooth muscle. Mutations in both the SUR1 and K IR 6.2 genes have been shown to cause familial hyperinsulinism, indicating the importance of the pancreatic β-cell channel in the regulation of insulin secretion. The availability of cloned K ATP channel genes opens the way for characterization of this family of ion channels and identification of additional genetic defects.