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Functions of the two types of calcium release channels in the sarcoplasmic reticulum of skeletal muscle.

Research Project

Project/Area Number 07457023
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionSaitama Medical School

Principal Investigator

ENDO Makoto  Saitama Med.Sch., Dept.Pharmacol., Prof., 医学部, 教授 (50009990)

Co-Investigator(Kenkyū-buntansha) IKEMOTO Takaaki  Saitama Med.Sch., Dept.Pharmacol., Instr., 医学部, 助手 (30275854)
KURAMOCHI Tomoya  Saitama Med.Sch., Dept.Pharmacol., Instr., 医学部, 助手 (10186497)
TAKESHIMA Hiroshi  Univ.Tokyo.Dept.Pharmacol., Assoc.Prof., 医学部, 助教授 (70212024)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1995: ¥4,500,000 (Direct Cost: ¥4,500,000)
Keywordscalcium release channel / type 1 ryanodine receptor / type 3 ryanodine receptor / Ca-induced Ca release (CICR) / sarcoplasmic reticulum / skeletal muscle / excitation-contraction coupling (EC coupling) / calmodulin / CaによるCa放出(CICR) / リアノジン受容体(骨格筋型) / リアノジン受容体(脳型) / 筋拘縮
Research Abstract

In the sarcoplasmic reticulum (SR) of frog skeletal muscle, two types of ryanodine receptors (calcium release channels) , corresponding to mammalian type 1 and type 3, respectively, are expressed in about equal amount. This study is aiming at elucidation of the physiological role of each of these two types of channels. We have obtained the following results. (1) The properties of type 3 channels were examined by using skeletal muscles of type 1-knockout mice that expresses only type 3 channels, and found to show Ca-induced Ca release (CICR) activity but require a higher Ca concentration for activation. (2) We made type 3-knockout mice, the skeletal mucle of which showed normal EC coupling. (3) only type 1 channel but neither type 2 nor type 3 channels can rescue impaired EC coupling in skeletal muscle of type 1-knockout mice. (4)We have been able to make mutant mice in which both type 1 and type 3 channels are knocked out. The SR of skeletal muscle of these mice can accumulate Ca but CICR is absent, indicating that in mouse skeletal muscle the expressed Ca release channels are only types 1 and 3, but not type 2. It was also found that "depolarization" -induced Ca release is the property of type 1 channels. (5) Calmodulin was found to enhance CICR at low activating concentration of Ca in addition to inhibition of CICR so far reported that is shown at higher activating concentrations of Ca. It shows mainly an enhancing effect on type 1 channels and an inhibitory effect on type 3 channels. (6) Ryanodine, which does not bind to closed channels, binds to channels open by physiological stimulation and fixes in an open state to cause contracture, in addition to the wellknown fact that it binds channels open by Ca (open in CICR mode). Therefore, it will be possible by using radioactive ryanodine, to determine the relative magnitude of opening of type 1 and 3 channel in physiological contraction.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Ikemoto, T., Iino, M.& Endo, M.: "Enhancing effect of calmodulin on Ca^<2+>-induced Ca^<2+> release in the sarcoplasmic reticulum of skeletal muscle fibres." Journal of Physiology. 487. 573-582 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takeshima, H., Yamazawa, T. et al.: "Ca^<2+>-induced Ca^<2+> release in myocytes from dyspedic mice lacking type-1 ryanodine receptor." EMBO Journal. 14. 2999-3006 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ikemoto, T., Iino, M.& Endo, M.: "Effect of calmodulin antagonists on calmodulin-induced biphasic modulation of Ca^<2+>-induced Ca^<2+> release." British Journal of Pharmacology. 118. 690-694 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takeshima, H., Ikemoto, T. et al.: "Generation and characterization of mutant mice lacking ryanodine receptor type 3." Journal of Biological Chemistry. 271. 19649-19652 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamazawa, T., Takeshima, H. et al.: "Subtype specificity of the ryanodine receptor for Ca^<2+> signal amplification in excitation-contraction coupling." EMBO Journal. 15. 6172-6177 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ikemoto, T., Komazaki, S. et al.: "Functions of the sarcoplasmic reticulum and morphological features of myocytes from mutant mice lacking both ryanodine receptors type 1 and type 3." Journal of Physiology. 501. 305-312 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Ikemoto, M.Iino & M.Endo: "Enhancing effect of calmodulin on Ca^<2+> induced Ca^<2+> release in the sarcoplasmic reticulum of skeletal muscle fibers." J.Physiol.487. 573-582 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Takeshima, T.Yamazawa, T.Ikemoto, H.Takekura, M.Nishi, T.Noda & M.Iino: "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
      1996 Final Research Report Summary
  • [Publications] T.Ikemoto, M.Iino & M.Endo: "Effect of calmodulin antagonists on calmodulin-induced biphasic modulation of Ca^<2+>-induced Ca^<2+> release." Brit.J.Pharmacol.118. 690-694 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Takeshima, T.Ikemoto, M.Nishi, N.Nishiyama, M.Shimuta, J.Kuno, I.Saito, H.Saito, M.Endo, M.Iino & T.Noda: "Generation and characterization of mutant mice lacking ryanodine receptor type 3." J.Biol.Chem. 271. 19649-19652 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Yamazawa, H.Takeshima, T.Sakurai, M.Endo & M.Iino: "Subtype specificity of the ryanodine receptor for Ca^<2+> signal amplification in excitation-contraction coupling." EMBO J.15. 6172-6177 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Ikemoto, S.Komazaki, H.Takeshima, M.Nishi, T.Noda, M.Iino, & M.Endo: "Functions of the sarcoplasmic reticulum and morphological features of myocytes from mutant mice lacking both ryanodine receptors type 1 and type 3." J.Physiol.501. 305-312 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 竹島浩: "Generation and characterization of mutant mice lacking ryanodine receptor type 3." Journal of Biological Chemistry. 270. 19649-196 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 池本隆昭: "Effect of calmodulin antagonists on calmodulin-induced biphasic modulation of Ca^<2+>-induced Ca^<2+> release." British Journal of Pharma cology. 118. 690-694 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 池本隆昭: "Functions of the sarcoplasmic reticulum and morphological features of myocytes from mutant mice lacking both ryanodine receptors type 1 and type 3." Journal of Physiology. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ikemoto,T., Iino,M.& Endo,M.: "Effect of calmodulin antagonists on calmodulin-induced biphasic modulation of Ca^<2+> -induced Ca^<2+> release." Br.J.Pharmacol.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ikemoto,T., Iino,M.& Endo,M.: "Enhancing effect of calmodulin on Ca^<2+> -induced Ca^<2+> release in the sarcoplasmic reticulum of skeletal muscle fibres." J.Physiol.487. 573-582 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takeshima,H., Yamazawa T., Ikemoto,T.et al.: "Ca^<2+> -induced Ca^<2+> release in myocytes from dyspedic mice lacking type-1 ryanodine receptor." EMBO J.14. 2999-3006 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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