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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				Y. Sato, M. Anello, and J.-C. Henquin Glucose Regulation of Insulin Secretion Independent of the Opening or Closure of Adenosine Triphosphate-Sensitive K+ Channels in {beta} Cells Endocrinology, May 1, 1999; 140(5): 2252 - 2257. [Abstract] [Full Text]

				A. Hambrock, C. Löffler-Walz, D. Kloor, U. Delabar, Y. Horio, Y. Kurachi, and U. Quast ATP-Sensitive K+ Channel Modulator Binding to Sulfonylurea Receptors SUR2A and SUR2B: Opposite Effects of MgADP Mol. Pharmacol., May 1, 1999; 55(5): 832 - 840. [Abstract] [Full Text]

				A. P. Babenko, G. Gonzalez, and J. Bryan Two Regions of Sulfonylurea Receptor Specify the Spontaneous Bursting and ATP Inhibition of KATP Channel Isoforms J. Biol. Chem., April 23, 1999; 274(17): 11587 - 11592. [Abstract] [Full Text] [PDF]

				L. Aguilar-Bryan and J. Bryan Molecular Biology of Adenosine Triphosphate-Sensitive Potassium Channels Endocr. Rev., April 1, 1999; 20(2): 101 - 135. [Abstract] [Full Text]

				K. Tanabe, S. J. Tucker, M. Matsuo, P. Proks, F. M. Ashcroft, S. Seino, T. Amachi, and K. Ueda Direct Photoaffinity Labeling of the Kir6.2 Subunit of the ATP-sensitive K+ Channel by 8-Azido-ATP J. Biol. Chem., February 12, 1999; 274(7): 3931 - 3933. [Abstract] [Full Text] [PDF]

				C. G. Vanoye, A. F. Castro, T. Pourcher, L. Reuss, and G. A. Altenberg Phosphorylation of P-glycoprotein by PKA and PKC modulates swelling-activated Cl- currents Am J Physiol Cell Physiol, February 1, 1999; 276(2): C370 - C378. [Abstract] [Full Text] [PDF]

				A. P. Babenko, G. Gonzalez, L. Aguilar-Bryan, and J. Bryan Reconstituted Human Cardiac KATP Channels : Functional Identity With the Native Channels From the Sarcolemma of Human Ventricular Cells Circ. Res., November 30, 1998; 83(11): 1132 - 1143. [Abstract] [Full Text] [PDF]

				E. L. Holmuhamedov, S. Jovanovic, P. P. Dzeja, A. Jovanovic, and A. Terzic Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function Am J Physiol Heart Circ Physiol, November 1, 1998; 275(5): H1567 - H1576. [Abstract] [Full Text] [PDF]

				S. Trapp, S. J. Tucker, and F. M. Ashcroft Mechanism of ATP-sensitive K Channel Inhibition by Sulfhydryl Modification J. Gen. Physiol., September 1, 1998; 112(3): 325 - 332. [Abstract] [Full Text] [PDF]

				K. N. Jew and R. L. Moore Exercise training alters an anoxia-induced, glibenclamide-sensitive current in rat ventricular cardiocytes J Appl Physiol, April 1, 2002; 92(4): 1473 - 1479. [Abstract] [Full Text] [PDF]

				A. P. Babenko, G. C. Gonzalez, and J. Bryan Hetero-concatemeric KIR6.X4/SUR14 Channels Display Distinct Conductivities but Uniform ATP Inhibition J. Biol. Chem., October 6, 2000; 275(41): 31563 - 31566. [Abstract] [Full Text] [PDF]

				M. Matsuo, K. Tanabe, N. Kioka, T. Amachi, and K. Ueda Different Binding Properties and Affinities for ATP and ADP among Sulfonylurea Receptor Subtypes, SUR1, SUR2A, and SUR2B J. Biol. Chem., September 8, 2000; 275(37): 28757 - 28763. [Abstract] [Full Text] [PDF]

				M. Matsuo, S. Trapp, Y. Tanizawa, N. Kioka, T. Amachi, Y. Oka, F. M. Ashcroft, and K. Ueda Functional Analysis of a Mutant Sulfonylurea Receptor, SUR1-R1420C, That Is Responsible for Persistent Hyperinsulinemic Hypoglycemia of Infancy J. Biol. Chem., December 22, 2000; 275(52): 41184 - 41191. [Abstract] [Full Text] [PDF]