PHYSIOLOGICAL REVIEWS   Vol. 78 No. 1 January 1998, pp. 227-245
Copyright ©1998 The American Physiological Society

Toward Understanding the Assembly and Structure of K_ATP Channels

LYDIA AGUILAR-BRYAN, JOHN P. CLEMENT IV, GABRIELA GONZALEZ, KUMUD KUNJILWAR, ANDREY BABENKO, AND JOSEPH BRYAN

Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, Texas

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_IR6.x) and sulfonylurea receptors (SUR), members of the ATP-binding cassette (ABC) superfamily. Recent studies indicate that SUR and K_IR6.x associate with 1:1 stoichiometry to assemble a large tetrameric channel, (SUR/K_IR6.x)₄ . The K_IR6.x subunits form the channel pore, whereas SUR is required for activation and regulation. Two K_IR6.x genes and two SUR genes have been identified, and combinations of subunits give rise to K_ATP channel subtypes found in pancreatic -cells, neurons, and cardiac, skeletal, and smooth muscle. Mutations in both the SUR1 and K_IR6.2 genes have been shown to cause familial hyperinsulinism, indicating the importance of the pancreatic -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.

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