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Molecular Mechanisms of Active Cross-bridge-dependent Regulation of Ca affinity of Cardiac Troponin

Research Project

Project/Area Number 10470010
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionThe Jikei University School of Medicine

Principal Investigator

KURIHARA Satoshi  Faculty of Medicine Physiology Professor, 医学部, 教授 (90057026)

Co-Investigator(Kenkyū-buntansha) FUKUDA Norio  Faculty of Medicine Physiology Research Associate, 医学部, 助手 (30301534)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Keywordscardiac muscle / troponin / Ca^<2+> / muscle length / cross-bridge / Ca affinity / Ca_<2+>
Research Abstract

We investigated molecular mechanisms which regulate cardiac muscle contraction using intact and skinned preparations. We measured the Ca transients and tension using aequorin which was injected into superficial cells of ferret papillary muscles. A decrease in muscle length from Lmax to 88%Lmax transiently increased intracellular Ca concentration (extra-Ca) in accordance with tension reduction. The normalized extra-Ca to intracellular Ca concentration before length reduction was increased in the solution with low Ca concentration and was reduced at higher Ca concentrations. Bay K 8644 decreased the normalized extra-Ca. These results suggest that an increase in intracellular Ca concentration increases the number of attached cross-bridges and this increases the Ca affinity of troponin C, resulting in the small normalized extra-Ca. We also measured pCa-tension relation using Triton X-100-treated skinned preparations and observed the muscle length-dependent shift of the relation. pCa-tension relation was shifted to the left at longer muscle lengths (length effect). In the presence of higher concentrations of H ion and phosphate, Ca responsiveness was decreased but length effect was enhanced. Thus, attachment of the cross-bridges is a critical factor for length-dependent change in Ca affinity of cardiac troponin C.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Fukuda N: "Effects of MgADP on length dependence of tension generation in skinned rat cardiac muscle"Circulation Research. 86. e1-e6 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S: "Effect of troponin I prosphorylation by protein kinase A on length-dependence of tension activation"Biochemical and Biophysical Research Communications. 272. 104-110 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S: "Logistic time constant of isometric relaxation force curve of terret ventricular papillary muscle : reliable index of Lusitropism"Japanese Journal Physiology. 50. 479-487 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 栗原敏: "フュレット心室筋トロポニンCのCa^<2+>親和性の張力依存性変化に対する細胞外Ca^<2+>濃度の影響"心筋の構造と代謝-1999-. 22. 215-217 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S: "Modulation of Ca^<2+> transient decay by tension and Ca^<2+> removal in hyperthyroid myocardium"American Journal Physiology. 276. H289-H299 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S: "Hybrid logistic characterization of isometric twitch force curve of isolated ferret right ventricular papillary muscle"Japanese Journal Physiology. 49(2). 145-158 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fukuda N: "Effects of pH on spontaneous tension oscillation in skinned bovine cardiac muscle"Pflugers Arch-European Journal of Physiology. 438. 125-132 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S: "Alterations in contractile properties and Ca^<2+> handling in streptozotocin-induced diabetic rat myocardium"American Journal of Physiology. 277. H2185-H2194 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S: "Effects of acidosis on Ca^<2+> sensitivity of contractile elements in intact ferret papillary muscles"American Journal of Physiology. 274. H145-H154 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S: "Estimation of myofibrillar responsiveness to Ca^<2+> in isolated rat ventricular myocytes"Pflugers Arch-European Journal of Physiology. 436. 639-645 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S: "Dynamic relations among length, tension, and intracellular Ca^<2+> in activated ferret papillary muscles"American Journal of Physiology. 275. H1957-H1962 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fukuda N.: "Effects of MgADP on length dependence of tension generation in skinned rat cardiac muscle."Circulation Research. 86. e1-e6 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S.: "Effect of troponin I phosphorylation by protein kinase A on length-dependence of tension activation."Biochemical and Biophysical Research Communications. 272. 104-110 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S.: "Logistic time constant of isometric relaxation force curve of ferret ventricular papillary muscle : reliable index of lusitropism."Japanese Journal of Physiology. 50. 479-487 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S.: "Responsiveness of contractile elements to muscle length in hyperthyroid ferret myocardium."In : The Hypertrophied Heart. eds. Takeda N, Nagano M, Dhalla NS.Kluwer Academic Publishers, Boston. 83-90 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S.: "Effects of extracellular Ca^<2+> on the tension-dependent change in Ca^<2+> affinity of cardiac troponin C in ferret ventricular muscles."Shinkin no Kouzou to Taisha-1999-22 (In Japanese). 215-217 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara S.: "Effects of adenine nucleotides on Ca^<2+> release from sarcoplasmic reticulum by rapid cooling."Shinkin no Kouzou to Taisha-1999-22 (In Japanese). 219-222 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fukuda N: "Effects of MgADP on legth dependence of tension generation in skinned rat cardiac muscle"Circulation Research. 86. e1-e6 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurihara S: "Effect of troponin I phosphorylation by protein kinase A on length-dependence of tension activation"Biochemical and Biophysical Research Communications. 272. 104-110 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurihara S: "Logistic time constant of isometric relaxation force curve of ferret ventricular papillary Muscle : reliable index of lusitropism"Japanese Journal Physiology. 50. 479-487 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 栗原敏: "フェレット心室筋トロポニンCのCa^<2+>親和性の張力依存性変化に対する細胞外Ca^<2+>濃度の影響"心筋の構造と代謝-1999-. 22. 215-217 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 栗原敏: "急速冷却による心筋小胞体Ca^<2+>放出に対するadenine nucleotidesの影響"心筋の構造と代謝-1999-. 22. 219-222 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurihara S: "The Hypertrophied Heart"Kluwer Academic Publishers. 83-90 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurihara,S.: "Hybrid logistic chaeacterization of ise metric twitch force curve of isolated ferret right ventricular papillary muscle"Japanese Journal of Physiology. 49. 145-158 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukuda,N.: "Effects of PM on spontaneous tension oscillation in skinned bovine cardiac muscle"Pfliigers Arch-European Journal of Physiology. 438. 125-132 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurihara,S.: "Alterations in contractile properties and Ca^<2+> handling in streptozotocin-induced diabetic rat myacardium"American Journal of Physiology. 277. M2185-M2194 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukuda,N.: "Effects of MgADP on length dependence of tension generation in skinned rat cardiac muscle"Circulation Research. 86. 1-6 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurihara,S: "Effects of acidosis on Ca_<2+> sensitivity of contractile elements in intact ferret papillary muscles." American Journal of Physiology. 274. H145-H154 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kurihara,S: "Dynamic relations among length, tension,and intracellular Ca_<2+> in activated ferret papillary muscles." American journal of physiology. 275. H1957-H1962 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 栗原 敏: "細胞内Ca_<2+>濃度変化による心筋の収縮制御とPDE阻害薬の作用機序" Lisa. 5. 54-64 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 栗原 敏: "糖尿病ラット心室筋の短縮とCa_<2+>transients" 心筋の構造と代謝. 20. 165-169 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kurihara,S: "Modulation of the Ca_<2+> transient decay by tension and Ca_<2+>removal in hyperthyroid myocardium." American Journal of Physiology. 276. 289-299 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 栗原 敏: "細胞実験法-2" 永野 允・今井昭一編, 573 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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