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Studies of inwardly rectifying K^+ channels and an approach to develop new methods for assaying K^+ channel activity.

Research Project

Project/Area Number 08557008
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General pharmacology
Research InstitutionOsaka University

Principal Investigator

HORIO Yoshiyuki  Osaka University Faculty of Medicine, Assosiate Professor, 医学部, 助教授 (30181530)

Co-Investigator(Kenkyū-buntansha) ISOMOTO Shojiro  Osaka University Faculty of Medicine, Assistant Professor, 医学部, 助手 (80273671)
TANEMOTO Masayuki  Osaka University Faculty of Medicine, Assistant Professor, 医学部, 助手 (40303945)
INANOBE Atsushi  Osaka University Faculty of Medicine, Assistant Professor, 医学部, 助手 (00270851)
YAMADA Mituhiko  Osaka University Faculty of Medicine, Assistant Professor, 医学部, 助手 (10263237)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1996: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordspotassium channel / glia / stomach / parietal cell / water channel / chromosome / patch clamp / sulfonylurea receptor / 内向き整流性カリウムチャネル / スルホニルウレア受容体 / クラスタリング / 網膜 / ミュラー細胞 / ラミニン / spatial buffering / パッチクランプ法 / RT-PCR / clustering / SAP97
Research Abstract

Inwardly rectifying K^+ channels (Kir channels) consist of more than 15 members and they are highy selective for K^+. They have, been estimated to possess two transmembrane domains and one pore-forming (H5) region. Amino acid sequence of H5 region of Kir channels has high similarity to each other and contains K^+ channel signature sequence of Gly-Tyr(Phe)-Gly. Each Kir channel consists of four subunits. Functions of Kir channels have been considered stabilizing and decreasing membrane potential, inhibiting excitability of cell, transport of K^+, and secretion of insulin. To evaluate Kir channel activity, patch-clamp method and measurement of influx of radioactive Rb have been used. But these methods have some defects. We planed to develop a new method to assay Kir channels, and at the same time, we planed to further study expression, distribution and function of Kir channels. Furthermore, we started to determine the chromosomal localization of some Kir channels to know the interaction of Kir channels and diseases. Our achievements are as follows. (1) Kir4.l/K_<AB>-2is expressed in glial cells and gastric parietal cells, the function of which is transport of K4. (2) new sulfonylurea receptor subunit (SUR2B) was cloned and identified as smooth vascular K_<ATP> channel subunit. (3) Kir3.2b, Kir1.lf, and cTBAK-1 were cloned. The chromosomal localization of Kir4.1/K_<Ab>-2, Kir5.1, Kir6.1, SUR2 and cTBAK-1 were identified. (4) We tried to develop measuring K^+ channel activity using PBFI.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Horio Y et al.: "Differential distribution of classical inwardly rectifying potassium channel mRNAs in the brain : Comparison of IRK2 with IRK1 and IRK3." FEBS Lett.379. 239-243 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Horio Y et al.: "Clustering and enhanced activity of an inwardly rectifying potassium channel, Kir4.1, by an anchoring protein, PSD-95/SAP 90 family." J.Biol.Chem.272. 12885-12888 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hibino H et al.: "An ATP-dependent inwardly rectifying potassium channel, KAB-2 (Kir4.1), in cochlear striavascularis of inner ear : its specific subcellular localization and correlation with the formation of endocochlear potential." J.Neurosci. 17. 4711-4721 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishii M et al.: "Expression and clustered distribution of an inwardly rectifying potassium channel, KAB-2/Kir4.1, on mammalian retinal Muller cell membrance ; Their regulation by insulin and laminin signals." J.Neurosci. 17. 7725-7735 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshimoto Y et al.: "Somatostatin induces hyperpolarization in pancreatic islet α cells by activating a G protein-gated K+ channel." FEBS Lett.444. 265-269 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagelhus E A et al.: "Immunogold evidence suggests that coupling of K+ siphoning and water transport in rat retinal Muller cells is mediated by a coenrichment of Kir4.1 and AQP4 in specific membrane domains." Glia. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kurachi et al.: "Potassium Channels : Molecular Structure, Function, and Diseases." Academic Press (in press),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Yoshimoto, Y.Fukuyama, Y.Horio, A.Inanobe, M.Gotoh, Y.Kurachi: "Somatostatin induces hyperpolarization in pancreatic islet alpha cells by activating a G protein-gated K^+ channel." FEBS Letters. 444. 265-269 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.Inanobe, Y.Yoshimoto, Y.Horio, K.Morishige, H.Hibino, S.Matsumoto, Y.Kurachi: "Characterization of G protein-gated K^+ channels composed of Kir3.2 subunits in substantia nigra." The Journal of Neuroscience. 19. 1006-1017 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] C.Kondo, VP.Repunte, E.Sato, M.Yamada, Y.Okuyama, Y.Horio, Y.Matsuzawa, L.Pott, Y.Kurachi: "Chimeras of Kir6.1 and Kir6.2 reveal structural elements invovled in spontaneous opening and unitary conductance of the classical ATP-sensitive K^+ channels." Receptors & Channels. 6/2. 129-140 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] E,Sato, M.Yamada, C.Kondo, Y.Okuyama, VP.Repunte Y.Horio, T.Iijima, Y.Kurachi: "Intracellular nucleotide-mediated gating of SUR/Kir6.0 complex potassium channels and its modification by pinacidil." The Journal of Physiology. 511.3. 663-674 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Shindo, M.Yamada, S.Isomoto, Y.Horio, Y.Kurachi: "SUR2 (A and B)-dependent differential activation of the cloned ATP-sensitive K+ channels by pinacidil and nicorandil." British Journal of Pharmacology. 124. 985-991 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Okuyama, M.Yamada, C.Kondo, E.Satoh, S.Isomoto, T.Shindo, Y.Horio, M.Kitakaze, M.Hori, Y.Kurachi: "Properties of SUR2A/Kir6.2 ATP-sensitive K+ channels expressed in a mammalian cell line, HEK 293T cells." Pflugers Archiv European Journal of Physiology. 435. 595-606 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] DH.Kim, A.Fujita, Y.Horio, Y.Kurachi.: "Molecular cloning and functional expression of a novel weak inward rectifier K+ channel with two pore domains predominantly expressed in heart." Circulation Research. 82. 513-518 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Ishii, Y.Horio, Y.Tada, H.Hibino, A.Inanobe, M.Ito, M.Yamada, T.Gotow, Y.Uchiyama, Y.Kurachi: "Expression and clustered distribution of an inwardly rectifying potassium channel, KAB-2/Kir4.1, on mammalian retinal Muller cell membrane : their regulation by insulin and laminin signals." The Journal of Neuroscience. 17(20). 7725-7735 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Hibino, Y.Horio, A.Inanobe, K.Doi, M.Yamada, T.Gotow, Y.Uchiyama, T.Kubo, Y.Kurachi.: "An ATP-dependent inwardly rectifying potassium channel, KAB-2(Kir4.1), in cochlear stria vascularis of inner ear : its specific subcellular localization and correlation with the formation of endocochlear potential." The Journal of neuroscience. 17(12). 4711-4721 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Horio, H.Hibino, A.Inanobe, M.Yamada, M.Ishi, Y.Tada, E.Satoh Y.Hata, Y.Takai, Y.Kurchi.: "Clustering and enhanced activity of an inwardly rectifying potassium channel, Kir4.1, by an anchoring protein, PSD-95/SAP 90 family." The Journal of Biological Chemistry. 272,20. 12885-12888 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Yamada, S.Isomoto, S.Matsumoto, C.Kondo, T.Shindo, Y.Horio, Y.Kurach.: "Sulfonylurea receptor 2B and Kir6.1 form a sulfonylurea-sensitive but ATP-insensitive+ channel." The Journal of Physiology. 499,3. 715-720 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Isomoto, C.Kondo, M.Yamada, S.Matsumoto, O.Higashiguchi, Y.Horio, Y.Matsuzawa, Y.Kurachi: "A novel sufonylurea receptor forms with BIR(Kir6.2) a smooth muscle type ATP-sensitive Kt channel." The Journal of General Physiology. 108. 485-495 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Ito, A.Inanobe, Y.Horio, S.Isomoto, H.Ito, K.Mori, A.Tonosaki, H.Tomoike, Y.Kurachi.: "Immunolocalization of an inwardly rectifying K+ channel, KAB-2 (Kir4.1), in the basolateral membrane of renal distal tubular epithelia." FEBS Letters. 388. 11-15 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Yamashita, Y.Horio, M.Yamada, N.Takahashi, C.Kondo, Y.Kurachi.: "Competition between Mg2+ and spermine for cloned IRK2 channel expressed in a human cell line." The Journal of Physiology. 493.1. 143-456 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Horio, K.Morishige, N.Takahashi, Y.Kurachi.: "Differential distribution of classical inwardly rectifying potassium channel mRNAs in the brain : comparison of IRK2 with IRK1 and IRK3." FEBS Letters. 379. 239-243 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshimoto Y et al.: "Somatostatin induces hyperpolarization in pancreatic islet α cells by activating a G protein-gated K+ channel." FEBS Lett.444. 265-269 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagelhus E A et al.: "Immunogold evidence suggests that coupling of K+ siphoning and water transport in rat retinal Miller cells is mediated by a coenrichment of Kir4.1 and AQP4 in specific membrane domains." Glia. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Tada: "Inwardly rectifying K+ channel in Muller cells:Comparison with the KAB-2/Kir4.1 channel expressed in HEK293T cells" Jpn.J.Physiol.48. 71-80 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Okuyama: "The effects of nucleotides and potassium channel openers on the SUR2A/Kir6.2 complex K+ channel expressed in a mammalian cell line,HEK293T cells" Pflugers Arch-Eur J.Physiol.435. 595-603 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Shindo: "SUR2 subtype(A and B)-dependent differential activation of the cloned ATP-sensitive K+ channels by pinacidil and nicorandil" Br.J.Pharmacol.124. 985-991 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] D.Kim: "Cloning and functional expression of a novel cardiac two-pore background K+ channel(cTBAK-1)" Circ Res.82. 513-518 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamada M, et all.: "Sulfonylurca receptor 2B and Kir6.1 form a sulfonilurca-sensitive but ATP-insensitive K+ channel." Journal of Physiology. 499. 715-720 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Horio Y, et al.: "Clustering and enhanced activity of an inwardly rectifying potassium channel,Kir4.1.by an anchoring protein,PsD-95/SAP 90 family." The Journal of Biological Chemistry. 272. 12885-12888 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hibino H, et al.: "An ATP-dependent inwardly rectifying potassium channel,KAB-2 (Kir4.1),in cochlear stria vascularis of inner ear : its specific subcellular localization and correlation with the formation of endocochlear potential." The Journal of Neuroscience. 17. 4711-4721 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Isomoto S, et al: "Sur2 and Kcnj8 genes are tightly linked on the distal region of mouse chromosome." Mammalian Genome. 8. 790-791 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishis M, et al.: "Expression and clustered distribution of an inwardly rectifying potassium channel,KAB-2/Kir4.1,on mammalian retinal miller cell membrane : Their Regulation by insulin and laminin signals." The Journal of Neuroscience. 17. 7725-7735 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tada Y, et al.: "Assignment of the glial inwardly rectifying potassium channel KAB-2/Kir4.1 (Kcnjl0) gene to the distal region of mouse chromosome 1." Genomics. 45. 629-630 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Okuyama Y, et al.: "Properties of SUR2A/Kir6.2 ATP-sensitive K+ channels expressed in a mammalian cell line,HEK 293T cells." Pfulers Archiv European Journal of Physiology. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kim DH, et al.: "Molecular cloning and functional expression of a novel weak inward rectifier K+ channel with two pore domains predominantly expressed in heart." Circulation Research. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Horio Y.: "Clustering and enhanced activity of an inwardly rectifying potassium channel,Kir4.1.by and anchoring protein,PSD-95/SAP 90 family." The Journal of Biological Chemistry. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hibino H.: "ATP-dependent inwardly rectifying potassium channel,K_<AB>-2 (Kir4.1),in cochlear stria vascularis of inner ear : its specific subcellular localization and correlation with the formation of endocochlear potential." The Journal of Neuroscience. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamada M.: "Sulfonylurea receptor 2B and Kir6.1 form a sulfonilurea-sensitive but ATP-insensitive K^+ channel." Journal of Physiology. 499. 715-720 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Horio Y.: "Differential distribution of claasical inwardly rectifying potassium channel mRNAs in the brain : comparison of IRK2 with IRK1 and IRK3." FEBS Letters. 379. 239-243 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Isomoto S.: "A novel ubiquitously-distributed isoform of GIRK2 (GIRK2B) enhances GIRK1-expression of the G-protein-gated K^+ current in Xenopus oocytes." Biochemical and Biophysical Research Communications. 218. 286-291 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamashita T.: "Competition between Mg^<2+> and spermine for cloned IRK2 channel expressed in a human cell line." Journal of Physiology. 493. 143-156 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ito M.: "Immunolocalization of an inwardly rectifying K^+ channel,K_<AB>-2 (Kir4.1),in the basolateral membrane of renal distal tubular epithelia." _FEBS Letters. 388. 11-15 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Isomoto S.: "A novel suofonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K^+ channel." The Journal of Biological Chemistry. 271. 24321-24324 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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