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Science 17 November 1995:
Vol. 270. no. 5239, pp. 1166 - 1170
DOI: 10.1126/science.270.5239.1166
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Research Articles

Reconstitution of I: An Inward Rectifier Subunit Plus the Sulfonylurea Receptor

Nobuya Inagaki (1),  Tohru Gonoi (1),  John P. Clement IV,  Noriyuki Namba,  Johji Inazawa,  Gabriela Gonzalez,  Lydia Aguilar-Bryan,  Susumu Seino (2),  Joseph Bryan

A member of the inwardly rectifying potassium channel family was cloned here. The channel, called BIR (Kir6.2), was expressed in large amounts in rat pancreatic islets and glucose-responsive insulin-secreting cell lines. Coexpression with the sulfonylurea receptor SUR reconstituted an inwardly rectifying potassium conductance of 76 picosiemens that was sensitive to adenosine triphosphate (ATP) (I) and was inhibited by sulfonylureas and activated by diazoxide. The data indicate that these pancreatic beta cell potassium channels are a complex composed of at least two subunits-BIR, a member of the inward rectifier potassium channel family, and SUR, a member of the ATP-binding cassette superfamily. Gene mapping data show that these two potassium channel subunit genes are clustered on human chromosome 11 at position 11p15.1.


N. Inagaki, N. Namba, and S. Seino are in the Division of Molecular Medicine, Center for Biomedical Science, Chiba University School of Medicine, Chuo-ku, Chiba 260, Japan. T. Gonoi is in the Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Chuo-ku, Chiba 260, Japan. J. P. Clement IV, G. Gonzalez, L. Aguilar-Bryan, and J. Bryan are in the Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, USA. J. Inazawa is in the Department of Hygiene, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602, Japan.
(1) These authors contributed equally to this study.
(2) To whom correspondence should be addressed.


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Physiol Rev 85, 319-371
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H3 Domain of Syntaxin 1A Inhibits KATP Channels by Its Actions on the Sulfonylurea Receptor 1 Nucleotide-Binding Folds-1 and -2.
N. Cui, Y. Kang, Y. He, Y.-M. Leung, H. Xie, E. A. Pasyk, X. Gao, L. Sheu, J. B. Hansen, P. Wahl, et al. (2004)
J. Biol. Chem. 279, 53259-53265
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Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features.
P. Proks, J. F. Antcliff, J. Lippiat, A. L. Gloyn, A. T. Hattersley, and F. M. Ashcroft (2004)
PNAS 101, 17539-17544
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Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) Genes Predict the Conversion from Impaired Glucose Tolerance to Type 2 Diabetes. The Finnish Diabetes Prevention Study.
O. Laukkanen, J. Pihlajamaki, J. Lindstrom, J. Eriksson, T. T. Valle, H. Hamalainen, P. Ilanne-Parikka, S. Keinanen-Kiukaanniemi, J. Tuomilehto, M. Uusitupa, et al. (2004)
J. Clin. Endocrinol. Metab. 89, 6286-6290
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Impact of Treatment on Islet Function in Type 2 Diabetes.
J.-C. Henquin, C. Boitard, E. Cerasi, E. Ferrannini, D. F. Steiner, and S. Efendic (2004)
Diabetes 53, S1-S5
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Metabolic Regulation of the Pancreatic Beta-Cell ATP-Sensitive K+ Channel: A Pas de Deux.
A. Tarasov, J. Dusonchet, and F. Ashcroft (2004)
Diabetes 53, S113-S122
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ATP-Sensitive K+ Channel Knockout Compromises the Metabolic Benefit of Exercise Training, Resulting in Cardiac Deficits.
G. C. Kane, A. Behfar, S. Yamada, C. Perez-Terzic, F. O'Cochlain, S. Reyes, P. P. Dzeja, T. Miki, S. Seino, and A. Terzic (2004)
Diabetes 53, S169-S175
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Roles of ATP-Sensitive K+ Channels as Metabolic Sensors: Studies of Kir6.x Null Mice.
K. Minami, T. Miki, T. Kadowaki, and S. Seino (2004)
Diabetes 53, S176-S180
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Syntaxin-1A Inhibits Cardiac KATP Channels by Its Actions on Nucleotide Binding Folds 1 and 2 of Sulfonylurea Receptor 2A.
Y. Kang, Y.-M. Leung, J. E. Manning-Fox, F. Xia, H. Xie, L. Sheu, R. G. Tsushima, P. E. Light, and H. Y. Gaisano (2004)
J. Biol. Chem. 279, 47125-47131
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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.
M. Yamada, M. Ishii, H. Hibino, and Y. Kurachi (2004)
Mol. Pharmacol. 66, 807-816
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Natriuretic Peptide Receptor-C Regulates Coronary Blood Flow and Prevents Myocardial Ischemia/Reperfusion Injury: Novel Cardioprotective Role for Endothelium-Derived C-Type Natriuretic Peptide.
A. Hobbs, P. Foster, C. Prescott, R. Scotland, and A. Ahluwalia (2004)
Circulation 110, 1231-1235
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Disruption of Glucose Sensing and Insulin Secretion by Ribozyme Kir6.2-Gene Targeting in Insulin-Secreting Cells.
L. Li, A. Rojas, J. Wu, and C. Jiang (2004)
Endocrinology 145, 4408-4414
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Fenofibrate, Troglitazone, and 15-Deoxy-{Delta}12,14-prostaglandin J2 Close KATP Channels and Induce Insulin Secretion.
K. Shimomura, H. Shimizu, M. Ikeda, S. Okada, M. Kakei, S. Matsumoto, and M. Mori (2004)
J. Pharmacol. Exp. Ther. 310, 1273-1280
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