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2005 Fiscal Year Final Research Report Summary

Molecular mechanisms for functional and spatial regulation of the G protein-gated potassium channel

Research Project

Project/Area Number 15209008
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionOsaka University

Principal Investigator

KURACHI Yoshihisa  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (30142011)

Co-Investigator(Kenkyū-buntansha) INANOBE Atsushi  Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (00270851)
HIBINO Hiroshi  Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (70314317)
ISHII Masaru  Osaka Minami Medical Center, Department of Clinical Research, Clinical Fellow, 免疫異常疾患研究所, 研究員 (10324758)
Project Period (FY) 2003 – 2005
KeywordsG protein-gated potassium channel / RGS protein / PDZ protein / Calmodulin / Lipid raft / FRET
Research Abstract

G protein-gated potassium (K_G) channels are under the control of receptor-dependent activation of G protein. This G protein-K_G channel system is negatively controlled by RGS (regulators of G protein signaling) proteins, which are normally inhibited by phosphatidyl-3,4,5-triphosphate (PIP_3) but can be activated (disinhibited) by Ca^<2+>/calmodulin (CaM) upon various biological stimulations (e.g., depolarization). The objective of the present study is to delineate molecular mechanisms underlying the functional regulation of K_G channels, and the following results were obtained. 1. RGS4 protein was expressed, purified and its interactions with phospholipids and CaM were investigated. It was demonstrated that (1)PIP_3 selectively bound to the RGS domain of RGS4, (2)the binding of PIP_3 to RGS4 was competitively displaced by Ca^<2+>/CaM and (3)the positively charged residues within the RGS domain seemed to be involved in the competitive binding between PIP_3 and CaM. 2.Molecular dynamics of RGS4 protein and CaM were further analyzed using FRET (Fluorescent resonance energy transfer) technique. It was demonstrated that (1)an elevation of intracellular Ca^<2+> concentration by ionomycin specifically increased the assembly of RGS protein and CaM in the living cells, but such increases were not observed (2)in the cells pre-treated with methyl-β-cyclodextrin, which depletes membrane cholesterol and disrupts lipid rafts or (3)in the cells expressing RGS4 mutant which lacks palmitoylation site necessary for the lipid raft-localization. The present study provide molecular basis for the reciprocal regulation of RGS protein by PIP_3 and CaM, which contribute to better understanding the molecular mechanisms for functional regulation of G protein- K_G channel system.

  • Research Products

    (31 results)

All 2006 2005 2004 2003

All Journal Article (30 results) Book (1 results)

  • [Journal Article] Carvedilol blocks cardiac KATP and KG but not IK1 channels by acting at the bundle-crossing regions.2006

    • Author(s)
      Kikuta J
    • Journal Title

      Eur J Pharmacol 529(1)

      Pages: 47-54

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels.2005

    • Author(s)
      Kubo Y
    • Journal Title

      Pharmacol Rev 57(4)

      Pages: 509-526

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular and cellular diversity of neuronal G-protein-gated potassium channels.2005

    • Author(s)
      Koyakh L
    • Journal Title

      J Neurosci 25(49)

      Pages: 11468-11478

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] In vivo interaction between RGS4 and calmodulin visualized with FRET techniques: possible involvement of lipid raft.2005

    • Author(s)
      Ishii M
    • Journal Title

      Biochem Biophys Res Commun 338(2)

      Pages: 839-846

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Gestational change of K+ channel opener effect is correlated with the expression of uterine KATP channel subunits.2005

    • Author(s)
      Sawada K
    • Journal Title

      Eur J Obstet Gynecol Reprod Biol 122(1)

      Pages: 49-56

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A functional role of the C-terminal 42 amino acids of SUR2A and SUR2B in the physiology and pharmacology of cardiovascular ATP-sensitive K^+ channels.2005

    • Author(s)
      Yamada M
    • Journal Title

      J Mol Cell Cardiol 39(1)

      Pages: 1-6

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Phosphatidylinositol 3, 4, 5-trisphosphate and Ca^<2+>/calmodulin competitively bind to the regulators of G-protein-signalling (RGS) domain of RGS4 and reciprocally regulate its action.2005

    • Author(s)
      Ishii M
    • Journal Title

      Biochem J 385(1)

      Pages: 65-73

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] In vivo interaction between RGS4 and calmodulin visualized with FRET techniques : possible involvement of lipid raft.2005

    • Author(s)
      Ishii M
    • Journal Title

      Biochem Biophys Res Commun 338(2)

      Pages: 839-846

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Phosphatidylinositol 3,4,5-trisphosphate and Cat^<2+>/calmodulin competitively bind to the regulators of G-protein-signalling (RGS) domain of RGS4 and reciprocally regulate its action.2005

    • Author(s)
      Ishii M
    • Journal Title

      Biochem J 385(1)

      Pages: 65-73

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Assays of RGS protein modulation by phosphatidylinositides and calmodulin.2004

    • Author(s)
      Ishii M
    • Journal Title

      Methods Enzymol 389

      Pages: 105-118

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of tertiapin on different types of recombinant inwardly rectifying potassium channels.2004

    • Author(s)
      Makino Y
    • Journal Title

      Med J Osaka Univ 47

      Pages: 1-11

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Comparison of kinetic properties of quinidine and dofetilide block of HERG channels.2004

    • Author(s)
      Tsujimae K
    • Journal Title

      Eur J Pharmacol 493(1-3)

      Pages: 29-40

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 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.2004

    • Author(s)
      Yamada M
    • Journal Title

      Mol Pharmacol 66(4)

      Pages: 807-816

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differential assembly of inwardly rectifying K^+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes.2004

    • Author(s)
      Hibino H
    • Journal Title

      J Biol Chem 279(42):

      Pages: 44065-44073

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ion channels: their structure, function and control an overview.2004

    • Author(s)
      Kurachi Y
    • Journal Title

      J Physiol 554(2)

      Pages: 245-247

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cell signal control of the G protein-gated potassium channel and its subcellular localization.2004

    • Author(s)
      Kurachi Y
    • Journal Title

      J Physiol 554(2)

      Pages: 285-294

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The nucleotide-binding domains of sulfonylurea receptor 2A and 2B play different functional roles in nicorandil-induced activation of ATP-sensitive K^+ channels.2004

    • Author(s)
      Yamada M
    • Journal Title

      Mol Pharmacol 65(5)

      Pages: 1198-1207

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of an inwardly rectifying K^+ channel, Kir5.1, in specific types of fibrocytes in the cochlear lateral wall suggests its functional importance in the establishment of endocochlear potential.2004

    • Author(s)
      Hibino H
    • Journal Title

      Eur J Neurosci 19(1)

      Pages: 76-84

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 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.2004

    • Author(s)
      Yamada M
    • Journal Title

      Mol Pharmacol 66(4)

      Pages: 807-816

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Differential assembly of inwardly rectifying K^+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes.2004

    • Author(s)
      Hibino H
    • Journal Title

      J Biol Chem 279(42)

      Pages: 44065-44073

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ion channels : their structure, function and control - an overview2004

    • Author(s)
      Kurachi Y
    • Journal Title

      J Physiol 554(2)

      Pages: 245-247

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cardiac conduction and arrhythmia: insights from Nkx2.5 mutations in mouse and humans.2003

    • Author(s)
      Jay PY
    • Journal Title

      Novartis Found Symp 250

      Pages: 227-238

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] International Union of Pharmacology. International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels.2003

    • Author(s)
      Gutman GA
    • Journal Title

      Pharmacol Rev 55(4)

      Pages: 583-586

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Physiological actions of regulators of G-protein signaling (RGS) proteins2003

    • Author(s)
      Ishii M
    • Journal Title

      Life Sci 74(2-3)

      Pages: 163-171

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Investigation of the optimal treatment strategy for atrial fibrillation in Japan.2003

    • Author(s)
      Yamashita T
    • Journal Title

      Circ J 67(9)

      Pages: 738-741

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differential expression and distribution of Kir5.1 and Kir4.1 inwardly rectifying K^+ channels in retina.2003

    • Author(s)
      Ishii M
    • Journal Title

      Am J Physiol Cell Physiol 285(2)

      Pages: C260-C267

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety, specifically inhibits pancreatic □-cell-type K_<ATP> channels.2003

    • Author(s)
      Chachin M
    • Journal Title

      J Pharmacol Exp Ther 304(3)

      Pages: 1025-1032

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cardiac conduction and arrhythmia : insights from Nkx2.5 mutations in mouse and humans.2003

    • Author(s)
      Jay PY
    • Journal Title

      Novartis Found Symp 250

      Pages: 227-238

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] International Union of Pharmacology. International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels : potassium channels.2003

    • Author(s)
      Gutman GA
    • Journal Title

      Pharmacol Rev 55(4)

      Pages: 583-586

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety, specifically inhibits pancreatic β-cell-type K_<ATP> channels.2003

    • Author(s)
      Chachin M
    • Journal Title

      J Pharmacol Exp Ther 304(3)

      Pages: 1025-1032

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 別冊 医学のあゆみ「イオンチャネルの最前線update2005

    • Author(s)
      倉智嘉久(編集)
    • Total Pages
      348
    • Publisher
      医歯薬出版株式会社. 2005
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2007-12-13  

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