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Investigation of pathophysiological properties of ion channels on cardiac sarcoplasmic reticulum.

Research Project

Project/Area Number 05044151
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionTokyo Medical and Dental University, Medical Research Institute

Principal Investigator

HIRAOKA Masayasu  Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (80014281)

Co-Investigator(Kenkyū-buntansha) KAWANO Seiko  Tokyo Medical and Dental University, Medical Research Institute, Assistant Profe, 難治疾患研究所, 助教授 (00177718)
CORONAD Roberts  Wisconsin University, Professor, 生理学教室, 教授
CORONADO Rob  ウィスコンシン大学, 生理学教室, 教授
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1994: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1993: ¥3,500,000 (Direct Cost: ¥3,500,000)
KeywordsRyanodine receptor Ca^<2+> release channel / sarcoplasmic reticulum / artificial lipid bilayr / Cl-channel / Cl-チャネル / リャノジン受容体チャネル / 小胞体 / 隣酸化
Research Abstract

(1) Investigation of regulatory mechanism of ryanodine receptor Ca^<2+> release channel. To investigate the regulatory mechanisms of ryanodine receptor Ca^<2+> release channel in cardiac sarcoplasmic reticulum (SR), we purified the SR membrane from pig hearts. These procedures were done in Dr.Coronado's lab at University of Wisconsin. The ryanodine receptors were incorporated into the artificial lipid bilayr and the channel activities were recorded by voltage clamp technique. Dr.Kawano and Dr.Hiraoka visited Dr.Coronado's lab to study and to discuss the procedure of purification of ryanodine receptors from pigs and bovine hearts. By using these preparations, we could record channel activities of ryanodine receptor. In this study we investigated Mg^<2+> effects on this channel and found that Mg^<2+> blocked the channel openings with diverse mechanisms. Namely, (1) Mg^<2+> reduced channel openings by competing with Ca^<2+> at the Ca^<2+> binding activating site of the channel and (2) by … More reducing the channel conductance.
Thus, we showed the detail regulatory mechanisms of Ca^<2+> release from SR by Mg^<2+>.
(2) Investigation of anion selectivity of a chloride channel in the porcine cardiac sarcoplasmic reticulum. We have reported that Cl-channel are present on cardiac sarcoplasmic reticulum which is activated by cyclic AMP dependent phosphorylation. In this study we examined the ion selectivity of this channel and compare the pore properties of this channel to those of other Cl-channels. Permeability ration calculated by Goldman-Hodgikin-Katz equation revealed the anion permeability sequence as Br->Cl->I->NO_3->F-. Those results were comparable to those of cystic fibrosis transmembrane regulator (CFTR) and the cardiac Cl-channel on the sarcolemma. The biophysical properties of this Cl-channel are very similar to those of the CFTR,suggesting the pore with a moderately high affinity site for anions. Therefor we speculate that cardiac SR Cl-channel may belong to the same family of Cl-channel as CFTR.Dr.Coronado found chloride-induced Ca^<2+> release from sarcoplasmic reticulum. Therefore, we had good discussions about the relationships between these channels on SR and Cl-channel. We could show the new signal tansduction pathway between channels on sarcolemma and those on SR,because of collaboration with Dr.Coronado. Less

Report

(2 results)
  • 1994 Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] S.Kawano: "Activation mechanism of 〔Ca^<2+>〕i sensitive transient outward current in rabbit ventricular myocytes." J.Physiol.(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Kawano: "Protein kinase A-activated chloride channel is inhibited by Ca^<2+> calmodulin complex in cardiac sarcoplasmic reticulum." Circ.Res.73. 751-757 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Kawano: "Direct effects of verapamil on the ryanodine receptor Ca^<2+> release channel of sarcoplasmic reticulum." Jpn.Circ.J.58. 458 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Hirayama: "Activation mechanism of calcium-sensitive transient outward current by intracellular calcium in rabbit ventricular myocytes." Jpn.Circ.J.58. 471 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Hirayama: "Ionic mechanism of calcium-sensitive transient outward current in rabbit ventricular myocytes." Jpn.Circ.J.58. 471 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Kawano: "Activation mechanism of the Ca^<2+> sensitive transient outward current by intracellular Ca^<2+> in rabbit ventricular myocytes." Jpn.J.Physiol.44. S75 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Kawano: "Activation mechanism of [Ca^<2+>] i-sensitive transiet outward current in rabbit ventricular myocytes." J.Physiol.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Kawano: "Protein kinase A-activated chloride channel is inhibited by Ca^<2+>/calmodulin complex in cardiac sarcoplasmic reticulum." Circ.Res.73. 751-757 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Kawano: "Direct effects of verapamil on the ryanodine receptor Ca^<2+> -release channel of sarcoplasmic retirulum." Jpn.Circ.J.58. 458 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Hirayama: "Activation mechanism of calcium-sensitive transient outward current by intracellular calcium in rabbit ventricular myocytes." Jpn.Circ.J.58. 471- (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Hirayama: "Ionic mechanism of calcium-sensitive transient outward current in rabbit ventricular myocytes." Jpn.Circ.J.58. 471- (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Kawano: "Activation mechanism of the Ca^<2+> sensitive transient outward current by intracellular Ca^<2+> in rabbit ventricular myocyte." 44. S75- (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kawano,S.: "Protein kinase A-activated chloride channel is inhibited by the Ca^<2+>-calmoduline complex in cardiac sarcoplsmic reticulum." Circulation Research. 73. 751-757 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hiraoka,M.: "Potassium channels in the heart." Cardiovascular Drug and Therapy. 7. 491-635 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 平岡昌和: "心筋のイオンチャネルの機能とその病態生理" Therapeutic Research. 14. 4965-4986 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 平岡昌和: "心筋イオンチャネルの活性化作用" Therapeutic Research. 14. 36-46 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 川野誠子: "心筋細胞の興奮・伝導とその異常" 図説病態内科学講座 循環器-1. 70-81 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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