TOWARD UNDERSTANDING THE ASSEMBLY AND STRUCTURE OF K-ATP CHANNELS

Adenosine 5'-triphosphate-sensitive potassium (K-ATP) channels couple metabolic events to membrane electrical cal activity in a variety of c ell types. The cloning and reconstitution of the subunits of these cha nnels demonstrate they are heteromultimers of inwardly rectifying pota ssium channel subunits (K(IR)6.X) and sulfonylurea receptors (SUR), me mbers of the ATP-binding cassette (ABC) superfamily. Recent studies in dicate that SUR and K(IR)6.X associate with 1:1 stoichiometry to assem ble a large tetrameric channel, (SUR/K(IR)6.x)(4) The K(IR)6.x subunit s form the channel pore, whereas SUR is required for activation and re gulation. Two K(IR)6.x genes and two SUR genes have been identified, a nd combinations of subunits give rise to K-ATP channel subtypes found in pancreatic beta-cells, neurons, and cardiac, skeletal, and smooth m uscle. Mutations in both the SUR1 and K(IR)6.2 genes have been shown t o cause familial hyperinsulinism, indicating the importance of the pan creatic beta-cell channel in the regulation of insulin secretion. The availability of cloned K-ATP channel genes opens the way for character ization of this family of ion channels and identification of additiona l genetic defects.