This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matsuoka, T. Articles by Kurachi, Y. Search for Related Content PubMed PubMed Citation Articles by Matsuoka, T. Articles by Kurachi, Y. Related Collections Electrophysiology Cardiovascular Pharmacology Ion channels/membrane transport

(Circulation Research. 2000;87:873.)
© 2000 American Heart Association, Inc.

Molecular Medicine

C-Terminal Tails of Sulfonylurea Receptors Control ADP-Induced Activation and Diazoxide Modulation of ATP-Sensitive K⁺ Channels

Tetsuro Matsuoka¹, Kenji Matsushita¹, Yusuke Katayama, Akikazu Fujita, Kiyoshi Inageda, Masayuki Tanemoto, Atsushi Inanobe, Shizuya Yamashita, Yuji Matsuzawa, Yoshihisa Kurachi

From the Departments of Pharmacology II (T.M., K.M., Y.K., A.F., K.I., M.T., A.I., Y.K.) and Internal Medicine and Molecular Science (T.M., S.Y., Y.M.), Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

Correspondence to Y. Kurachi, Department of Pharmacology II, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail ykurachi{at}pharma2.med.osaka-u.ac.jp

Abstract—The ATP-sensitive K⁺ (K_ATP) channels are composed of the pore-forming K⁺ channel Kir6.0 and different sulfonylurea receptors (SURs). SUR1, SUR2A, and SUR2B are sulfonylurea receptors that are characteristic for pancreatic, cardiac, and vascular smooth muscle–type K_ATP channels, respectively. The structural elements of SURs that are responsible for their different characteristics have not been entirely determined. Here we report that the 42 amino acid segment at the C-terminal tail of SURs plays a critical role in the differential activation of different SUR-K_ATP channels by ADP and diazoxide. In inside-out patches of human embryonic kidney 293T cells coexpressing distinct SURs and Kir6.2, much higher concentrations of ADP were needed to activate channels that contained SUR2A than SUR1 or SUR2B. In all types of K_ATP channels, diazoxide increased potency but not efficacy of ADP to evoke channel activation. Replacement of the C-terminal segment of SUR1 with that of SUR2A inhibited ADP-mediated channel activation and reduced diazoxide modulation. Point mutations of the second nucleotide-binding domains (NBD2) of SUR1 and SUR2B, which would prevent ADP binding or ATP hydrolysis, showed similar effects. It is therefore suggested that the C-terminal segment of SUR2A possesses an inhibitory effect on NBD2-mediated ADP-induced channel activation, which underlies the differential effects of ADP and diazoxide on K_ATP channels containing different SURs.

Key Words: K_ATP channel • sulfonylurea receptor • C-terminus • ADP • diazoxide

This article has been cited by other articles:

				E. Procko, M. L. O'Mara, W. F. D. Bennett, D. P. Tieleman, and R. Gaudet The mechanism of ABC transporters: general lessons from structural and functional studies of an antigenic peptide transporter FASEB J, May 1, 2009; 23(5): 1287 - 1302. [Abstract] [Full Text] [PDF]

				A. Wheeler, C. Wang, K. Yang, K. Fang, K. Davis, A. M. Styer, U. Mirshahi, C. Moreau, J. Revilloud, M. Vivaudou, et al. Coassembly of Different Sulfonylurea Receptor Subtypes Extends the Phenotypic Diversity of ATP-sensitive Potassium (KATP) Channels Mol. Pharmacol., November 1, 2008; 74(5): 1333 - 1344. [Abstract] [Full Text] [PDF]

				M. A. Burke, R. K. Mutharasan, and H. Ardehali The Sulfonylurea Receptor, an Atypical ATP-Binding Cassette Protein, and Its Regulation of the KATP Channel Circ. Res., February 1, 2008; 102(2): 164 - 176. [Abstract] [Full Text] [PDF]

				F. M. Ashcroft ATP-sensitive K+ channels and disease: from molecule to malady Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E880 - E889. [Abstract] [Full Text] [PDF]

				P. Tammaro, P. Proks, and F. M. Ashcroft Functional effects of naturally occurring KCNJ11 mutations causing neonatal diabetes on cloned cardiac KATP channels J. Physiol., February 15, 2006; 571(1): 3 - 14. [Abstract] [Full Text] [PDF]

				M. Yamada, M. Ishii, H. Hibino, and Y. Kurachi Mutation in Nucleotide-Binding Domains of Sulfonylurea Receptor 2 Evokes Na-ATP-Dependent Activation of ATP-Sensitive K+ Channels: Implication for Dimerization of Nucleotide-Binding Domains to Induce Channel Opening Mol. Pharmacol., October 1, 2004; 66(4): 807 - 816. [Abstract] [Full Text] [PDF]

				J. Tamargo, R. Caballero, R. Gomez, C. Valenzuela, and E. Delpon Pharmacology of cardiac potassium channels Cardiovasc Res, April 1, 2004; 62(1): 9 - 33. [Abstract] [Full Text] [PDF]

				M. Chachin, M. Yamada, A. Fujita, T. Matsuoka, K. Matsushita, and Y. Kurachi Nateglinide, a D-Phenylalanine Derivative Lacking Either a Sulfonylurea or Benzamido Moiety, Specifically Inhibits Pancreatic beta -Cell-Type KATP Channels J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1025 - 1032. [Abstract] [Full Text] [PDF]

				E. A. Cartier, S. Shen, and S.-L. Shyng Modulation of the Trafficking Efficiency and Functional Properties of ATP-sensitive Potassium Channels through a Single Amino Acid in the Sulfonylurea Receptor J. Biol. Chem., February 21, 2003; 278(9): 7081 - 7090. [Abstract] [Full Text] [PDF]

				M. Suzuki, T. Saito, T. Sato, M. Tamagawa, T. Miki, S. Seino, and H. Nakaya Cardioprotective Effect of Diazoxide Is Mediated by Activation of Sarcolemmal but Not Mitochondrial ATP-Sensitive Potassium Channels in Mice Circulation, February 11, 2003; 107(5): 682 - 685. [Abstract] [Full Text] [PDF]

				S. Poitry, L. van Bever, F. Coppex, A. Roatti, and A. J Baertschi Differential sensitivity of atrial and ventricular KATP channels to metabolic inhibition Cardiovasc Res, February 1, 2003; 57(2): 468 - 476. [Abstract] [Full Text] [PDF]

				P. J Hanley, M. Mickel, M. Loffler, U. Brandt, and J. Daut KATP channel-independent targets of diazoxide and 5-hydroxydecanoate in the heart J. Physiol., August 1, 2002; 542(3): 735 - 741. [Abstract] [Full Text] [PDF]

				M. Dabrowski, F. M. Ashcroft, R. Ashfield, P. Lebrun, B. Pirotte, J. Egebjerg, J. Bondo Hansen, and P. Wahl The Novel Diazoxide Analog 3-Isopropylamino-7-Methoxy-4H-1,2,4-Benzothiadiazine 1,1-Dioxide Is a Selective Kir6.2/SUR1 Channel Opener Diabetes, June 1, 2002; 51(6): 1896 - 1906. [Abstract] [Full Text] [PDF]

				J. P. Giblin, Y. Cui, L. H. Clapp, and A. Tinker Assembly Limits the Pharmacological Complexity of ATP-sensitive Potassium Channels J. Biol. Chem., April 12, 2002; 277(16): 13717 - 13723. [Abstract] [Full Text] [PDF]

				L. V. Zingman, D. M. Hodgson, M. Bienengraeber, A. B. Karger, E. C. Kathmann, A. E. Alekseev, and A. Terzic Tandem Function of Nucleotide Binding Domains Confers Competence to Sulfonylurea Receptor in Gating ATP-sensitive K+ Channels J. Biol. Chem., April 12, 2002; 277(16): 14206 - 14210. [Abstract] [Full Text] [PDF]

				K. Matsushita, K. Kinoshita, T. Matsuoka, A. Fujita, T. Fujikado, Y. Tano, H. Nakamura, and Y. Kurachi Intramolecular Interaction of SUR2 Subtypes for Intracellular ADP-Induced Differential Control of KATP Channels Circ. Res., March 22, 2002; 90(5): 554 - 561. [Abstract] [Full Text] [PDF]

				K. Matsushita, K. Kinoshita, T. Matsuoka, A. Fujita, T. Fujikado, Y. Tano, H. Nakamura, and Y. Kurachi Intramolecular Interaction of SUR2 Subtypes for Intracellular ADP-Induced Differential Control of KATP Channels Circ. Res., March 22, 2002; 90(5): 554 - 561. [Abstract] [Full Text] [PDF]