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THE MECHANISM OF ANTI-ARRHYTHMIC EFFECT OF Mg^<2+> UNDER Ca^<2+> OVERLOAD

Research Project

Project/Area Number 04670528
Research Category

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

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionHAMAMATSU UNIVERSITY SCHOOL OF MEDICINE

Principal Investigator

KOBAYASHI Akira  Hamamatsu Uni.Internal Med.Associate Professor, 医学部, 助教授 (00096588)

Co-Investigator(Kenkyū-buntansha) TERADA Hajime  Hamamatsu Uni.Internal Med.Research Associate, 医学部, 助手 (50252177)
HAYASHI Hideharu  Hamamatsu Uni.Photon Me.Res.Cen.Associate Professor, 光量子医学研究センター, 助教授 (50135258)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsMAGNESIUM / CALCIUM OVERLOAD / CALCIUM WAVES / ANTIARRHYTHMIC EFFECT / CALCIUM TRANSIENT / CAFFEINE / VERAPAMIL / TRIGGERED ACTIVITY / Ca^<2+>transient / Mgnesium / Calcium wave / Arrhythmia
Research Abstract

The arrythmias caused by Ca^<2+> overload have been suggested to be due to the triggered activities resulting from the spontaneous Ca^<2+> release from sarcoplasmic reticulum (SR). The phenomenon that the discrete region of elevated [Ca^<2+>]i travels along a myocyte is called the Ca^<2+> wave and is frequently observed under Ca^<2+> overloaded state. In this study, it was shown that raising the Mg^<2+> concentration of solution inhibited the Ca^<2+> wave with minimal suppression of electrically induced Ca^<2+> transient. The effect of Mg^<2+> was contrasted with the effect of verapamil, which inhibited the Ca^<2+> wave with the suppression of electrically induced Ca^<2+> transient. High Mg^<2+> solution also suppressed the Ca^<2+> wave in rested myocyte. These results suggested that the suppression of Ca^<2+> wave by Mg^<2+> was not related to the voltage dependent Ca^<2+> channel blocking property. To examine whether the effect of Mg^<2+> is exserted intracellulally, the effect of raising the Mg^<2+> concentration of solution on the [Mg^<2+>]i was examined. It was shown that raising the Mg^<2+> concentration increased the [Mg^<2+>]i with smilar time course to the suppression of Ca^<2+> wave. Since an increase in [Mg^<2+>]i has been reported to activate the Ca^<2+>-ATPase of SR and to inhibit Ca^<2+> releasing channel of SR, the amount of releasable Ca^<2+> in SR was estimated using post-rest and caffeine-induced C2+ transient as an index. Both post-rest and caffeine-induced Ca^<2+> transient were increased by high Mg^<2+> solution. These results suggested that antiarrythmic effect of Mg^<2+> is not due to the inhibition of voltage dependent Ca^<2+> channel, but due to an increase in Ca^<2+> holding capacity of SR.Since Mg^<2+> suppressed Ca^<2+> wave with minimal inhibition of electrically induced Ca<

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Noda H.,Hayashi H.,Kobayashi A.: "Cytosolic Ca2+ concentration and pH of diabetic rat myocytes during metabolic inhibition." J.Mol.Cell.Cardiol.24. 435-446 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hayashi H.,Kobayashi A.: "Intracellular Ca2+ concentration and pHi during metabolic inhibition" Am.J.Physiol.262. C628-C634 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Noda N.,Terada H.,Hayashi H.: "Effects of Mg2+ on “Ca2+ wave"and Ca2+ transients of rat ventricular myocytes" J.Mol.Cell.Cardiol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 寺田肇.野田直久.佐藤洋.宮田勝夫.山崎昇.林秀晴.小林明: "Ca^<2+>過負荷時の不整脈に対するMg^<2+>の抗不整脈作用の機序の検討-ラット心室筋細胞における高Mg^<2+>溶液のCa^<2+>waveと細胞内Mg^<2+>濃度に及ぼす影響" Therapeutic Res. 14. 421-423 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Satoh H.,Hayashi H.,Kobayashi A.: "Regulation of [Na+]i and [Ca2+]i in guinea pig myocytes:dual loading of fluorescent indicators SBFI and fluo 3." Am.J.Physiol(Heart Circ Physiol 35). 266(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Noda, H., Hayashi, H., Miyata, H., Suzuki, S., Kobayashi, A., Yamazaki, N.: "Cytosolic Ca2+ concentration and pH of diabetic rat myocytes during metabolic inhibition." Molecular and Cellular Cardiology. 24(4). 435-446 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hayashi, H., Miyata, H., Noda, N., Kobayashi, A., Hirano, M., Kawai, T., Yamazaki, N.: "Intracellular Ca2+ concentration and pHi during metabolic inhibition." Am.J.Physiol.262(Cell Physiology 31). C628-C634 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Terada, H., Noda, N., Satoh, H., Miyata, H., Kobayashi, A., Yamazaki, N., Hayashi, H.: "The mechanism of anti-arrhythmic effect of Mg2+ under Ca2+ overload - Effects of Mg2+ on "Ca2+ wave" and Ca2+ transients of rat ventricular myocytes.(in Japanese)" Therapeutic Res.14(2). 421-423 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Satoh, H., Hayashi, H., Noda, N., Terada, H., Kobayashi, A., Hirano, M., Yamashita, Y., Yamazaki, N.: "Regulation of [Na+]i and [Ca2+]i in guinea pig myocytes : dual loading of fluorescent indicators SBFI and fluo 3." Am.J.Physiol.266(Heart Circ.Physiol.35). H568-H576 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 寺田肇・野田直久・佐藤洋・小林明・山崎昇・林秀晴: "ラット心室筋細胞のCa^<2+>waveと細胞内Mg^<2+>濃度に及ぼす高Mg^<2+>溶液の効果" Japanese Circulation Journal. 57(saplw). 218 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 寺田 肇: "Ca^<2+>過負荷時の不整脈に対するMg^<2+>の抗不整脈作用の機序の検討ーラット心室筋細胞における高Mg^<2+>溶液のCa^<2+> waveと細胞内Mg^<2+>濃度に及ぼす影響ー" Therapeutic Research. 14. 421-423 (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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