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Intracellular Ca^<2+> regulation in the myocardium with ryanodine receptor type 2(+/-) heterozygous mouse

Research Project

Project/Area Number 13670048
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

KURIHARA Satoshi  Jikei University, School of Medicine, Professor, 医学部, 教授 (90057026)

Co-Investigator(Kenkyū-buntansha) OTSU Kinya  Osaka University, Graduate School of Medicine Dept.of Internal Medicine and Therapeutics, Research Assistant, 医学系研究科・医学部, 助手 (20294051)
KUSAKARI Yoichiro  Jikei University, School of Medicine, Research Assistant, 医学部, 助手 (80338889)
HONGO Kenichi  Jikei University, School of Medicine, Lecturer, 医学部, 講師 (00256447)
田中 悦子  東京慈恵会医科大学, 医学部, 講師 (70256410)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsintracellular Ca^<2+> / myocardium / ryanodine receptor type2 / mouse / SERCA2a / Ca^<2+> transient / isoprenaline / acidosis / Ca^<2+>トランジェント / マウス心室筋 / 細胞内Ca transient / 張力 / Caポンプ / SERCA / 収縮蛋白系 / 遺伝子非改変マウス / エクオリン
Research Abstract

We produced knockout mouse with ryanodine receptor type 2 (RyR-2(+/-)) and explored the cardiac functions of the heart. In Langenforff perfusion, we could not detect any significant changes of the parameters of pressure (dP/dt, -dP/dt) and end diastolic volume in the heart in K.O. mouse. We concluded that the partial deletion of RyR-2 is well compensated. Then, we focused on the Ca^<2+> pump of sarcoplasmic reteiculum (SERCA2a) which plays an important role in the regulation of [Ca^<2+>]i. We overexpressed SERCA 2a (TG) and explored its cardiac functions. In TG, &P/dt and-dP/dt were larger than those in nonTG (NTG). In TG, cardiac hypertrophy was significantly reduced when the heart was loaded with higher pressure. Thus, SERCA2a plays a key role to improve pathophysiological adaptation. We dissected papillary muscles from the left ventricle of TO and measured Ca^<2+> transient(CaT) with aequorin. The peak of CaT was larger than that of NTG. The time courses of CaT in TG were faster than those in NTG. In NTG, isoprenaline increased the peak of CaT and shortened the time course of CaT. However, no significant changes of these parameters were observed in TO. In CO_2 acidosis, contraction was decreased although CaT was increased in NTG. In TO, similar changes were observed but the inhibition of contraction in acidosis was reduced. The recovery of contraction was also better than that in NTG. Thus, SERCA2a plays a pivotal role under pathophysiological condition.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] 栗原 敏: "エクオリンを用いた心筋細胞内Ca^<2+>信号の測定"Japanese Journal Electrocardiology. 21. s-2-3-s-2-14 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 福田紀男: "Ca^<2+>感受性決定機構"Clinical Calcium. 11(6). 13-19 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hongo K: "Use of Tetanus to Investigate Myofibrillar Responsiveness to Ca^<2+> in Isolated Mouse Ventricular Myocytes."Japanese Journal Physiology. 52. 121-127 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kusakari Y: "The Mechanism of an Increasing in Ca^<2+> Responsiveness by α_1-Adrenergic Stimulation in Rat Ventricular Myocytes."Jpn J Physiol. 52(6). 531-539 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mio Y: "Bupivacaine Attenuates Contractility by Decreasing Sensitivity of Myofilaments to Ca^<2+> in Rat Ventricular Muscle."Anesthesiology. 97(5). 1168-1177 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakayama H: "Cardiac-specific overexpression of high Ca^<2+> affinity mutant of SERCA2a attenuates in vivo pressure overload cardiac hypertrophy."FASEB J. 17(1). 61-63 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Asahi M: "Regulation of Sarco(endo)plasmic Reticulum Ca^<2+> Adenosine Triphosphatase by Phospholamban and Sarcolipin ; Implication for Cardiac Hypertrophy and Failure."Trends Cardiovasc Med. 13(4). 152-157 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 草刈洋一郎: "不全心における収縮障害の細胞内メカニズム-SERCA2aを中心として-"日本薬理学雑誌. 123(2). 87-93 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kongo K: "Signal Transduction and Cardiac Hypertrophy"Kluwer Academic Publishers. 508 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kurihara S: "Measurement of intracellular Ca^<2+> signal in cardiac muscles using aequorin."Japanese Journal Electrocardiology. 21. S-2-3-S-2-14 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukuda N: "Regulation of Ca^<2+> Sensitivity of Contractile Elements in Cardiac Muscle."Clinical Calcium. 11(6). 13-19 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hongo K: "Use of Tetanus to Investigate Myofibrillar Responsiveness to Ca^<2+> in Isolated Mouse Ventricular Myocytes."Japanese Journal Physiology. 52. 121-127 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kusakari Y: "The Mechanism of an Increase in Ca^<2+> Responsiveness by α1-Adrenergic Stimulation in Rat Ventricular Myocytes."Jpn J Physiol. 52(6). 531-539 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mio Y: "Bupivacaine Attenuates Contractility by Decreasing Sensitivity of Myofilaments to Ca^<2+> in Rat Ventricular Muscle."Anesthesiology. 97(5). 1168-1177 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakayama H: "Cardiac-specific overexpression of high Ca^<2+> affinity mutant of SERCA2a attenuates in vivo pressure overload cardiac hypertrophy."FASEB J. 17(1). 61-63 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Asahi M: "Regulation of Sarco(endo)plasmic Reticulum Ca^<2+> Adenosine Trip hosphatase by Phospholamban and Sarcolipin : Implication for Cardiac Hypertrophy and Failure."Trends Cradiovasc Med. 13(4). 152-157 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kusakari Y: "The mechanism of contractile dysfunction in heart failure, focussing on SERCA2a function."Nippon Yakurigaku Zassi. 123(2). 87-93 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakayama H: "Cardiac-sepcific overexpression of high Ca^<2+> affinity mutant of SERCA2 a attenuates in vivo pressure overload cardiac hypertrophy."FASEB J. 17(1). 61-63 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Asahi M: "Regulation of Sarco(endo)Plasmic Reticulum Ca^<2+> Adenosine Triphosphatase by Phospholamban and Sarcolipin : Implication for Cardiac Hypertrophy and Failure."Trends Cardiovasc Med.. 13(4). 152-157 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 草刈 洋一郎: "不全心における収縮障害の細胞内メカニズム-SERCA2aを中心として-"日本薬理学雑誌. 123(2). 87-93 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hongo K: "Signal Transduction and Cardiac Hypertrophy"Kluwer Academic Publishers. 508 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakayama H: "Cardiac-specific overexpression of high Ca^<2+> affinity mutant of SERCA2a attenuates in vivo pressure overlaod cardiac hypertrophy"FASEB J. 17(1). 61-63 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kusakari Y: "The mechanism of an increase in Ca^<2+> responsiveness by α1-adrenergic stimulation in rat ventricular myocytes"Jpn J Physiol. 52(6). 531-539 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mio Y: "Bupivacaine attenuates contractility by decreasing sensitivity of myofilaments to Ca^<2+> in rat ventricular muscle"Anesthesiology. 97(5). 1168-1177 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hongo K: "Use of tetanus to investigate myofibrillar responsiveness to Ca^<2+> in isolated mouse ventricular myocytes"Jpn J Physiol. 52. 121-127 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hoshida S: "Repeated Physiologic stresses provide persistent cardioprotection against ischemia-reperfusion injury in rats"J Am Coll Cardiol. 40(4). 826-831 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hongo K: "Signal Transduction and Cardiac Hypertrophy"Kluwer Academic Publishers (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Yagi N: "Cross-bridge and calcium behavior in ferret papillary muscle different thyroid states"Japanese Journal Physiology. 51. 319-326 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukuda N: "Length dependence of tension generation in rat skinned cardiac muscle-Role of titin in the Frank-Starling mechanism of the heart"Circulation. 104. 1639-1645 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukuda N: "Acidosis or inorganic phosphate enhances the length dependence of tension in rat skinned cardiac muscle"Journal Physiology. 536. 153-160 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 栗原 敏: "エクオリンを用いた心筋細胞内Ca^<2+>信号の測定"Japanese Journal Electrocardiology. 21. S-2-3-S-2-14 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 福田 紀男: "Ca^<2+>感受性決定機構"Clinical Calcium. 11(6). 13-19 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hongo K: "Use of tetanus to investigate myofibrillar responsiveness to Ca^<2+> in isolated mouse ventricular myocytes"Japanese Journal Physiology. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hongo K: "Signal Transduction and Cardiac Hypertrophy"Kluwer Academic Publishers (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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