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Molecular biological studies of ryanodine receptor/calcium release channel

Research Project

Project/Area Number 06454150
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field General physiology
Research InstitutionSaitama Medical School

Principal Investigator

TAKESHIMA Hiroshi  Saitama Medical School, Faculty of Medicine, Lecturer, 医学部, 講師 (70212024)

Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1994: ¥5,700,000 (Direct Cost: ¥5,700,000)
Keywordscalcium release channel / intracellular calcium / ryanodine / muscle contraction / caffeine
Research Abstract

The aim of this research is elucidating physiological functions of teh ryanodine receptor/calcium ralease channel in a whole animallevel. Thus, we first tried to find or generate mutant animals in the ryanodine receptor gene. Because so many mutants are known in fruit fly system, we analyzed a ryanodine receptor gene in Drosophila melanogaster and the chromosomal mapping was done (FEBS) Lett. 337,81) ; however, no mutant is known at the located chromosomal position. Then, we tried to prepare mutnat mice lacking the skeletal muscle ryanodine receptor using embyonic stem cells. In the first analysis of the generated mutant mice, we showed that the skeletal muscle ryanodine receptor is an essential molecule for muscle maturation and excitation-contraction coupling (Nature 369,556). An electron-microscopy found triad juctions with a narrow size between transverse-tuble and sarcoplasmi reticulum membranes in the mutnat muscle, indicationg that the skeletal muscle ryanodine receptor determines the size between the membranes but is not essential for generation of the junction (Proc.Natl.Acad.Sci.USA.92,3391). Moreover, we found expression of the brain-type of ryanodine receptor in mutant muscle, and revealedits pharmoacological properties accompanying inability to contribute skeletal muscle exicitation-conrtraction couplina (EMBO J.14,2999).
In summary, we defined the phisiological function of the skeletal muscle ryanodine receptor by generation and analysis of knockout mice, and showed the differential role between ryanodine receptor shbtypes.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] 竹島ら他6名: "Isolation and charactevization of a gene for a vyanodine veceptor in Drosophila welavogaster" FEBS Lattevs. 337. 81-87 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 竹島ら他4名: "Abnovewal jcuction baoween supface wewbvane and sarcoplasunic reticulum in skeletal wuscle will a targeted to the rupvodire vesepts" Proc. Natl. Acad. Sci. U.S.A.92. 3381-3385 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 竹島ら他7名: "Excitation-coatvaction uncoupling and wusclelar degenevation in mice lacking functional skeletal wuscle ryciroding receptor gana." Natuve. 369. 556-559 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 竹島ら他6名: "Ca^<2+>-induced Ca^<2+>relecse in myocytes from aqspedic wice lacking type^<-1> ryanodine" EMBO J.14. 2999-3006 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 竹島ら他9名: "ブレインサイエンス最前線'96" 講談社サイエンティフィック, 129ページ (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takeshima, H., Nishi, M., Iwabe, N., Miyata, T., Hosoya, T., Masai, I.& Hotta, Y.: "Isolation and characterization of a gene for a ryanodine receptor/calcium release channel in Drosophila melanogaster" FEBS Lett. 337. 81-87 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fududa, K., Kato, S., Mori, K., Nishi, M., Takeshima, H., Iwabe, N., Miyata, T., Houtani, T.& Sugimoto, T: "cDNA cloning and regional distribution of a novel member of the opioid receptor family" FEBS Lett.343. 42-46 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takeshima, H., Iino, M., Takekura, H., Nishi, M., Kuno, J., Minowa, O., Takano, H.& Noda, T.: "Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene" Nture. 369. 556-559 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Houtani, T., Ueyama, T., Takeshima, H., Kato, S., Fukuda, K., Mori, K.& Sugimoto, T: "mu Opioid receptor : expression and vagotomyinduced depletioin of the mRNA in medullary preganglionic neurons." Mol.Brain Res. 24. 1-4 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Furuichi, T., Furutami, D., Hakamata, Y., Nakai, J., Takeshima, H.& Mikoshiba, K.: "Multiple types of ryanodine receptor/calcium release channels are differnitially experssed in rabbit brain." J.Neurosci. 14. 4794-4805 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nishi, M., Takeshima, H., Mori, M., Nakagawara, K.& Takeuchi, T.: "Structure and chromosomal mapping of genes for the mouse k-opioid receptor and an opioid receptor homologue (MOR-C)." Biochem.Biophys.Res.Commun. 205. 1353-1357 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takekura, H., Nishi, M., Noda, T., Takeshima, H.& FranziniArmstrong, C.: "Abnormal junctions between surface membrane and sarcoplasmic reticulum in skeletal muscle with a mutation targeted to the ryanodine receptor." Proc.Natl.Acad.Sci.USA.92. 3381-3385 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sun, X-H., Protasi, F., Takahashi, M., Takeshima, H., Feguson, D.G., Franzini-Armstrong, C.: "Molecular archiecture of membranes involved in excitation-cotraction coupling of cardiac muscle." J.Cell Biol. 129. 659-671 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ueda, H., Miyame, T., Fukushima, N., Takeshima, H., Fukuda, K., Sasaki, Y.& Misu, Y.: "Opioid mu-and k-receptor mediate phospholipase C activation through Gil in Xenopus oocytes." Mol.Brain Res. 32. 166-170 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takeshima, H., Yamazawa, T., Ikemoto, T., Takekura, H., Nishi, M., Noda, T.& Iino, M.: "Ca^<2+>-induced Ca^<2+> release in myocytes from dyspedic mice lacking type-1 ryanodine receptor." EMBO J. 14. 2999-3006 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takekura, H., Takeshima, H., Nishimura, S., Takahashi, M., Tanabe, T., Flockerzi, V., Hofmann, F.& Franzini-Armstrong, C.: "Co-expression in CHO cells of two muscle protein involved in excitation-contraction coppling." J.Muscle Res.Cell Motil. 16. 465-480 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Houtani, T., Nishi, M., Takeshima, H., Nukada, T.& Sugimoto, T.: "Structure and regional distribution of nociceptin/orphanin FQ precursor." Biochem.Biophys.Res.Commun.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 竹倉ら 他4名: "Abnormal junction between surface membrane and sarcoplasmic resticulum in skeletal muscle with a targeted mutation to the ryanodine receptor" Proc.Natl.Acad.Sci.U.S.A.92. 3,381-3,385 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sunら 他5名: "Molecular architecture of membranes involved in excitation-contraction coupling of cordiac muscle" J.Cell Biol.129. 659-671 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 竹島ら 他6名: "Ca^<2+>-induced Ca^<2+> release in myocytes from dyspedic mice lacking type-1 ryanodine receptor" EMBO J.14. 2,999-3,006 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 竹倉ら 他7名: "Co-expression in cHO cells of two muscle protein involved in excitation-contraction coupling." J.Muscle Res.Cell Motil.16. 465-480 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 竹島浩: "骨格筋型リアノジン受容体欠損マウスにおける興奮収縮連関の欠失と筋退縮" 実験医学. 13. 455-458 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 竹島浩: "ジーンターゲッテングによるリアノジン受容体の機能解析" 生化学. 67. 209-294 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 竹島浩 ら他9名: "ブレインサイエンス最前線'96" 講談社 サイエンティフィク社, 129 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 竹島ら 他6名: "Isolation and characterization of a geue for a ryauodine receptor in Drosophila welanogasle" FEBS Letters. 337. 81-87 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 竹島ら 他7名: "Excitation-coutraction uucouping and muscular degeneration in mice locking functional skeletel muscle ryanodine receptor gune" Nature. 369. 556-559 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 古市ら 他5名: "Multiple types of ryanodine receptor/calcium release channels are differentially expressed in rabbit brain." Journal of Neuroscience. 14. 4794-4805 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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