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1998 Fiscal Year Final Research Report Summary

Molecular Mechanism in Regulation of Inwardly Rectifying Potassium Channel and its Functional Disorder

Research Project

Project/Area Number 07407006
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionOsaka University

Principal Investigator

KURACHI Yoshisa  Osaka University Faculty of Medicine, Professor, 医学部, 教授 (30142011)

Co-Investigator(Kenkyū-buntansha) TANEMOTO Masayuki  Osaka University Faculty of Medicine, Assistant Professor, 医学部, 助手 (40303945)
INANOBE Atsuhi  Osaka University Faculty of Medicine, Assistant Professor, 医学部, 助手 (00270851)
HORIO Yoshiyuki  Osaka University Faculty of Medicine, Associate Professor, 医学部, 助教授 (30181530)
Project Period (FY) 1995 – 1998
KeywordsInwardly rectifying K+channel / 2 membrane spanning K+channel / ATP sensitive K+channel / G-protein regulated K+channel / Anchering protein / Sulffonylurea receptor / Central Nervous System / Hormone
Research Abstract

(1) ATP sensitive potassium channels
A) We cloned a new sulfonylurea receptor(SUR2b) and revealed it forms a smooth muscle type ATP sensitive K+channel with Kir6.1. ATP sensitive K+channel is reported to be regulated by intracellular nucleotides and K+channel openers. We found out that the regulation of the ATP sensitive K+channel is different according to the difference of the channel forming units.
B) We made several chimeras between Kir6.1 and Kir6.2, and by using these chimeras we revealed that the pore-forming region of the channel is responsible for determining channel conductance. Furthermore we found out the amino acids Ser (113), Ile (114), His (115), and Val (138) are major determinant of channel conductance of Kir6.2.
(2) G-protein regulated potassium channels
A) We revealed G-protein regulated K+channel of dopaminergic neurons in substancia nigra (SN) is composed from channel subunits, Kir3.2a and Kir3.2c. We also revealed SAP97, one of the members of anchering proteins which h … More ave PSD domains, is also expressed with these K+ channels.
B) We showed Kir3.1 and Kir3.4 are expressed on the membrane of secretary vesicles in TSH secreting cells of pituitary body. By stimulating these cells with agonists, functional K+channels is expressed on the plasma membrane after fusion of secretary vesicles to the plasma membrane.
C) We cloned a new subunit of G-protein regulated K+channel, Kir3.lb. This clone is a spliced variant of Kir3.la (former reported as Kir3.1). Checking the function of this clone, we showed strong evidence that C-terminal portion of Kir3.1 is indespensable for the channel activation by G-protein.
(3) other potassium channels
A) Kir2.Os are expressed on different cells in olfactory bulb (GB). This cell-specific expression of each channel units might indicate the functional specificity of them in the olfactory sensory system.
B) In CNS, Kir4.1 (Kirl.2) was distributed especially on the basolateral membrane of epithelium of inner lymph follicle, glial cells, and ependymal cells. In retina, it is expressed on Muller cells. These specific distribution of this channel reflects a functional importance of Kir4.1 in handling potassium ions between different ional milieus.
C) We also cloned new four membrane spanning K+channel (CTBAK) from heart cDNA library. Less

  • Research Products

    (47 results)

All Other

All Publications (47 results)

  • [Publications] K.Morishige: "Exocytosis of secretary granules inserts ion channels into the plasma membrane" The Journal of Biological Chemistry. in press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Yoshimoto: "Somatostation induces hyperpolarization in pancreatic islet α G protein-gated K+ channel." FEBS Letters. in press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] EA. Nagelhus: "Subcellular coexpression of the inwardly rectifying K+ channel Kir4.1 and water aquaporin-4 in retinal muller cells suggests coupling between K+ siphoning and water transport." Glia. in press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Inanobe: "Characterization of G protein-gated K+ channels composed of KIr3.2 subunits in substantia nigra" The Journal of Neuroscience. 19(3). 1006-1017 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Hambrock: "Mg2+ and ATP dependence of KATP channel modulator binding to the recombinant receptor, SUR2B." British Journal of Phatmacology. 125. 577-583 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] C.Kondo: "Chimeras of Kir6.1 and Kir6.2 reveal structural elements invovled in spontaneous opening and unitary conductance of the classical ATP-sensitive K+ chemistry" Receptors & Channels. 6(2). 129-140 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] E.Sato: "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(和文)」より
  • [Publications] T.Shindo: "SUR2 subtype (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(和文)」より
  • [Publications] Y.Okuyama: "properties of SUR2A/Kir6.2 ATP-sensitive K+ channels expressed in a mammalian cell line, HEK 293T cells" 〓flugers Archiv European Journal of Physiology. 435. 595-603 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] DH.Kim: "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(和文)」より
  • [Publications] Y.Ohta: "Identification and functiona analysis of sulfonylurea receptor 1 variants in Japanese patients with NIDDM." Diabetes. 47. 476-481 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Ishii: "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(和文)」より
  • [Publications] H.Hibino: "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(和文)」より
  • [Publications] Y.Horio: "Clustering and enhanced activity of inwardly rectifying potassium channel, Kir4.1, by an anchoring protein, PSD-95/SAP90 family" The Journal of Biological Chemistry. 272(20). 12885-12888 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Yamada: "Sulfonylurea receptor 2B and Kir6.1 form a sulfonilurea-sensitive but ATP-insensitive K+channel" The Journal of Physiology. 499(3). 715-720 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Ito: "Phosphorylation-independent inhibition by intracellular cyclic nucleotides of brain inwardly rectifying K+ current expressedin Xenopus oocytes." FEBS Letters. 402. 12-16 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] C.Kondo: "Cloning and functional expression of a novel isoform of ROMK inwardly rectifying ATP-dependent K+ channel, ROMK6 (Kir1.1f)." FEBS Letters. 399. (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Hosoya: "A functional model for G protein activation of the muscarimic K+ channel in guinea pig atrial myocytes : Spectral analysis of the effect of GTP on single-channel kinetics." The Journal of General Physiology. 108. 485-495 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Isomoto: "A novel suofonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel." The Journal of Biological Chemistry. 271(40). 24321-24324 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Ito: "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(和文)」より
  • [Publications] T.Yamashita: "Competition between Mg2+ and spermine for cloned IRK2 channel expressed in a human cell line" The Journal of Physiology. 493(1). 143-156 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Hazama: "Neurokinin A and Ca2+ current induce Ca2+-activated Cl-currents in guinea-pig tracheal myocytes." The Journal of Physiology. 492(2). 377-393 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A Terzic: "Actin microfilament-distrupters activate KATP chanels by antagonizing ATP-dependent gating in patches from Guinea-pig cardiomyocytes" The Journal of Physiology. 492(2). 395-404 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Horio: "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(和文)」より
  • [Publications] T.Nakajima: "17β Estradiol inhibits the voloage-dependent L-type Ca2+ currents in aortic smooth muscle cells." European Jounral of Pharmacology. 294. 625-635 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Nakajima: "Ionic basis of neurokinin A-induced depolarization in single smooth muscle cells isolated from the guinea pig trachea." Pflugers Archiv European Journal of Physiology. 430. 552-562 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Takumi: "A novel ATP-dependent inward rectifier potassium channel expressed predominantly in glial cells" The Journal of Biological Chemistry. 270(27). 16339-16346 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Yamada: "Spermine gates inward-rectifying muscarinic but not ATP-sensitive K+ channels in rabbit atrial myocytes : intracellular substance-mediated mechanism of inward rectification" The Journal of Biological Chemistry. 270(16). 9289-9294 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Morishige, A.Inanobe, H.Kurachi, A.Miyake, Y.Murata, Y.Tokunaga, T.Maeda, Y.Kurachi: "Exocytosis of secretary granules inserts ion channels into the plasma membrane." The Journal of Biological Chemistry. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [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. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Inanove, 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. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [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
  • [Publications] T.Shindo, M.Yamada, S.Isomoto, Y.Horio, Y.Kurachi.: "SUR2 (A and B)-dependent differential activationo f 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
  • [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
  • [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 heat." Circulation Research. 82. 513-518 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [Publications] H.Hibino, T.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
  • [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
  • [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
  • [Publications] Y.Hosoya, M.Yamada, H.Ito, Y.Kurachi.: "A functional model for G protein activation of the muscarinic K+ channel in guimea pig atrial myocytes : Spectral and lysis of the effect of GTP on single-channel kinetics." The Journal of Physiology. 108. 485-495 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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 K+ channel." The Journal of Biological Chemistry. 271. 24321-24324 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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 basolatral 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
  • [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
  • [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
  • [Publications] T.Takumi, T.Ishii, Y.Horio, K.Morishige, N.Takahashi, M.Yamada, T.Yamashita, H.Kiyama, K.Sohmiya, S.Nakanishi, Y.Kurachi: "A novel ATP-dependent inward rectifiler potassium channel expressed predominantly in glial cells." The Journal of Biological Chemistry. 270. 16339-16346 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Yamada, Y.Kurachi.: "Spermine gates inward-rectifying muscarinic but not ATP-sensitive K+ channels in rabbit atrial myocytes : intracellular substance-mediated mechanism of inward rectification." The Journal of Biological Chemistry. 270. 9289-9294 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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