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Molecular mechanism of contractile dysfunction and the alteration of intracellular Ca^<2+> handling caused by mutation of cardiac troponin T

Research Project

Project/Area Number 19500357
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurophysiology and muscle physiology
Research InstitutionJikei University School of Medicine

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) HONGO Kenichi  東京慈恵会医科大学, 医学部, 准教授 (00256447)
KOMUKAI Kimiaki  東京慈恵会医科大学, 医学部, 講師 (60360145)
SASAKI Hiroyuki  東京慈恵会医科大学, 医学部, 准教授 (60170693)
FUKUDA Norio  東京慈恵会医科大学, 医学部, 講師 (30301534)
MORIMOTO Sachio  九州大学, 医学研究科, 准教授 (50202362)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords心筋 / トロポニンT / Ca^<2+>感受性 / アンギオテンシンII受容体 / Ca^<2+> / トロポニン / 細胞内Ca^<2+> / 筋小胞体 / Ca感受性 / 拡張型心筋症 / Caトランジェント / アンギオテンシンII / DCM / マウス / 細胞内Ca / Ca transient / レニン・アンギオテンシン系 / 心エコー / Ca 感受性 / 細胞内Ca2^<2+> / CaMKII
Research Abstract

We explored the mechanism of pathogenesis and sudden death in dilated cardiomyopathy using knock-in mouse model with mutant troponin T (DCM mouse). DCM mouse died suddenly from age of 1 month old. In DCM mouse, cardiac chamber was dilated and contractile functions were impaired. A blocker of angiotensin II receptor (ARB) significantly increased survival rate and improved the cardiac functions without changing the decreased Ca^<2+> sensitivity in DCM mouse. ARB also improved the fibrosis and electrocardiogram, which were considered as critical for the beneficial effects of ARB.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (46 results)

All 2010 2009 2008 2007

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (32 results)

  • [Journal Article] Titin and troponin : central players in the Frank-Starling mechanism ofthe heart.2009

    • Author(s)
      Fukuda N, Terui T, Ohtsuki I, Ishiwata S, Kurihara S
    • Journal Title

      Current Cardiology Reviews 5(2)

      Pages: 119-124

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Half-logistic time constants as inotropic and lusitropic indices for four sequential phases of isometric tension curves in isolated rabbit and mouse papillary muscles.2009

    • Author(s)
      Mizuno J, Morita S, Otsuji M, Arita H, Hanaoka K, Robert E, Hirano S, Kusakari Y, Kurihara S
    • Journal Title

      Int Heart J 50(3)

      Pages: 389-404

    • NAID

      130000120823

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protein kinase A-dependent modulation of Ca2+ sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin2009

    • Author(s)
      Matsuba D, Terui T, O-Uchi J, Tanaka H, Ojima T, Otsuki I, Ishiwata, Kurihara S, Fukuda N
    • Journal Title

      J Gen Physiol 133(6)

      Pages: 571-581

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protein kinase A-dependent phosphorylation of ryanodine receptors increases Ca2+ leak in mouse heart2009

    • Author(s)
      Morimoto S, O-Uchi J, Kawai M, Hoshina T, Kusakari Y, Komukai K, Sasaki H, Hongo K, Kurihara S
    • Journal Title

      BBRC 390

      Pages: 87-92

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] 左室圧、張力、筋細胞内カルシウムトランジェントのハイブリッド・ロジスティック関数を用いた波形解析による収縮弛緩過程の推定2009

    • Author(s)
      水野樹、森田茂穂、大辻幹哉、花岡一雄、栗原敏
    • Journal Title

      臨床麻酔 33(9)

      Pages: 1479-1488

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Titin and troponin : central players in the Frank-Starling mechanism of the heart.2009

    • Author(s)
      Fukuda N, Terui T, Ohtsuki I, Ishiwata S, Kurihara S
    • Journal Title

      Current Cardiology Reviews 5(2)

      Pages: 119-124

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Half-logistic time constants as inotropic and lusitropic indices for four sequential phases of isometric tension curves in isolated rabbit and mouse papillary muscles.2009

    • Author(s)
      Mizuno J, Morita S, Otsuji M, Arita H, Hanaoka K, Robert E, Hirano S, Kusakari Y, kurihara S
    • Journal Title

      Int Heart J 50(3)

      Pages: 389-404

    • NAID

      130000120823

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein kinase A-dependent modulation of Ca^<2+> sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin.2009

    • Author(s)
      Matsuba D, Terui T, O-Uchi J, Tanaka H, Ojima T, Otsuki I, Ishiwata, Kurihara S, Fukuda N
    • Journal Title

      J.Gen.Physiol. 133(6)

      Pages: 571-581

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein kinase A-dependent phosphorylation of ryanodine receptors increases Ca^<2+> leak in mouse heart.2009

    • Author(s)
      Morimoto S, O-Uchi J, kawai M, Hoshina T, Kusakari Y, Komukai K, Sasaki H, Hongo K, Kurihara S
    • Journal Title

      BBRC 390

      Pages: 87-92

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 左室圧、張力、筋細胞内カルシウムトランジェントのハイブリッド・ロジスティック関数を用いた波形解析による収縮弛緩過程の推定2009

    • Author(s)
      水野樹, 森田茂穂, 大辻幹哉, 花岡一雄, 栗原敏
    • Journal Title

      臨床麻酔 33(9)

      Pages: 1479-1488

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of alpha1-adrenoceptor subtypes with different G proteins induces opposite effects on cardiac L-type Ca2 channel2008

    • Author(s)
      O-Uchi J, Sasaki H, Morimoto S, Kusakari Y, Shinji H, Obata T, Hongo K, Komukai K, Kurihara S
    • Journal Title

      Circ Res 102(11)

      Pages: 1378-1388

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Physiological functions of the giant elastic protein titin in mammalian striated muscle2008

    • Author(s)
      Fukuda N, Granzier HL, Ishiwata S, Kurihara S
    • Journal Title

      J Physiol Sci 58(3)

      Pages: 151-159

    • NAID

      10022598046

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of alphal-adrenoceptor subtypes with different G proteins induces opposite effects on cardiac L-type Ca^<2+>channel.2008

    • Author(s)
      O-Uchi J, Sasaki H, Morimoto S, Kusakari Y, Shinji H, Obata T, Hongo K, Komukai K, Kurihara S
    • Journal Title

      Circ Res. 102(11)

      Pages: 1378-88

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Physiological functions of the giant elastic protein titin in mam malian striated muscle.2008

    • Author(s)
      Fukuda N, Granzier HL^<1)>, Is hiwata S^<2)>, Kurihara S. (<^1)> Department of Molecular, Cellular Biology, University of Arizona, <2)>^Department of Physics, Waseda University)
    • Journal Title

      J Physiol Sci. 58(3)

      Pages: 151-9

    • NAID

      10022598046

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Single sarcomere imaging in cardiomyocytes with quantum dots(QDOTS) : physiological significance of spoc in cardiac beat.2010

    • Author(s)
      Fukuda N, Serizawa T, Shintani S, Terui T, Ishiwata S, Kurihara S
    • Organizer
      Biophysical Society 54^<th> Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] Single sarcomere imaging by quantum dots(QDOTS) in the heart.2010

    • Author(s)
      Terui T, Shintani S, Ishiwata S, Kurihara S, Fukuda N
    • Organizer
      Biophysical Society 54^<th> Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] Renin-angiotensin system plays an important role in the pathogenesis of DCM in mouse2009

    • Author(s)
      Hongo K, Morimoto S, O-Uchi J, Kusakari Y, Komukai K, Kawai M, Yoshimura M, Morimoto S, Ohtsuki I, Takeda N, Kurihara S
    • Organizer
      The XXXVI International Congress of Physiological Sciences
    • Place of Presentation
      京都
    • Related Report
      2009 Final Research Report
  • [Presentation] Endothelin-1 potentiates L-type Ca2+ current by activating CaMKII in rat ventricular myocytes2009

    • Author(s)
      Komukai K, O-uchi J, Morimoto S, Kawai M, Hongo K, Yoshimura M, Kurihara S
    • Organizer
      The XXXVI International Congress of Physiological Sciences
    • Place of Presentation
      京都
    • Related Report
      2009 Final Research Report
  • [Presentation] β-Adrenoceptor stimulation increased Ca2+ leak from sarcoplasmic reticulum without dissociation of FKBP12. 6 under physiological condition2009

    • Author(s)
      Morimoto S, O-uchi J, Kawai M, Komukai K, Sasaki H, Yoshimura M, Hongo K, Kurihara S
    • Organizer
      The XXXVI International Congress of Physiological Sciences
    • Place of Presentation
      京都
    • Related Report
      2009 Final Research Report
  • [Presentation] Thin filament-based regulation of length-dependent activation in skinned porcine ventricular muscle2009

    • Author(s)
      Terui T, Shimamoto Y, Sodnomtseren M, Yamane M, Ohtsuki I, Ishiwata S, Kurihara S, Fukuda N
    • Organizer
      The XXXVI International Congress of Physiological Sciences
    • Place of Presentation
      京都
    • Related Report
      2009 Final Research Report
  • [Presentation] トロポニン再構成によるFrank-Starling機構の分子メカニズムの解明2009

    • Author(s)
      照井貴子、福田紀男、大槻磐男、上園晶一、栗原敏
    • Organizer
      日本麻酔科学会第56回学術集会
    • Place of Presentation
      神戸
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] Endothelin-1 increases L-type Ca2+ current of rat ventricular myocytes via an activation of protein kinase C and Ca2+/calmodulin dependent protein kinaseII2009

    • Author(s)
      Komukai K, O-Uchi J, Hongo K, Kawai M, Morimoto S, Yoshimura M, Kurihara S
    • Organizer
      American Heart Association
    • Place of Presentation
      Orlando, USA
    • Related Report
      2009 Final Research Report
  • [Presentation] Rennin-angiotensin system plays an important role in the pathogenesis of DCM in mouse.2009

    • Author(s)
      Hongo K, Morimoto S, O-uchi J, Kusakari Y, Komukai K, Kawai M, Yoshimura M, Morimoto S, Ohtsuki I, Takeda N, Kurihara S
    • Organizer
      The XXXVI International Congress of Physiological Sciences
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] Endothelin-1 potentiates L-type Ca current by activating CaMKII in ratventricular myocytes.2009

    • Author(s)
      Komukai K, O-uchi J, Morimoto S, Kawai M, Hongo K, Yoshimura M, Kurihara S
    • Organizer
      The XXXVI International Congress of Physiological Sciences
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] Na^+, Mg^<2+>, and adenine nucleotides modulate the Ca^<2+->. caffeine^-, and rapid cooling- induced Ca^<2+> release in skinned ferret cardiac muscles.2009

    • Author(s)
      Tanaka E, Kurihara S
    • Organizer
      The XXXVI International Congress of Physiological Sciences
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] β-Adrenoceptor stimulation increased Ca leak from sarcoplasmic reticulum without dissociation of FKBP12.6 under physiological condition.2009

    • Author(s)
      Morimoto S, O-uchi J, Kawai M, Komukai K, Sasaki H, Yoshimura M, Hongo K, Kurihara S
    • Organizer
      The XXXVI International Congress of Physiological Sciences
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] Thin filament-based regulation of length-dependent activation in skinned porcine ventricular muscle.2009

    • Author(s)
      Terui T, Shimamoto Y, Sodnomtser-en M, Yamane M, Ohtsuki I, Ishiwa-ta S, Kurihara S, Fukuda N
    • Organizer
      The XXXVI International Congress of Physiological Sciences
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] Endothelin-1 increases L-type Ca current of rat ventricular myocytesvia an activation of protein kinase C and ca/calmodulin dependent protein kinase II.2009

    • Author(s)
      Fiomukai K, O-uchi J, Hongo K, Kawai M, Morimoto S, Yoshimura M, Kurihara S
    • Organizer
      American Heart Association
    • Place of Presentation
      Orlando, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] Role of thin filament cooporative activation in length-dependentactivation in skinned porcine ventricular muscle.2009

    • Author(s)
      Terui T, Shimamoto Y^<1)>, Sodnomtseren M^<1)>, Yamane M^<1)>Ohtsuki I, Ishiwata S^<1)>, Kurihara s, Fukuda N(<1)>WasedaUniversity)
    • Organizer
      Biophysical Society 53rd Annual Meeting
    • Place of Presentation
      Boston, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Protein kinase A-based modulation of Ca^<2+> sensitivity in skinnedskeletal muscle fibers reconstituted with cardiac troponin.2009

    • Author(s)
      Fukuda N, Matsuba D, Terui T, 0-Uchi J, Tanaka H^<1)>, Ojima T <1)>, Ohtsuki I, Ishiwata S^<2)>, Kurihara S(<1>)Hokkaido University, ^<2)>Waseda University)
    • Organizer
      Biophysical Society 53rd Annual Meeting
    • Place of Presentation
      Boston, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Aipha_<1A>-adrenoceptor stimulation inhibits L-type Ca^<2+> current in the presence of B- adrenoceptor stimulation in rat ventricular myocytes.2008

    • Author(s)
      O-Uchi J*, Kurihara S(University of Rochester)
    • Organizer
      Upstate New York cardiac electrophysiology society eighteenth annual meeting.
    • Place of Presentation
      Buffalo, USA.
    • Year and Date
      2008-10-20
    • Related Report
      2008 Annual Research Report
  • [Presentation] Thin filament-based regulation of length dependent activation in skinned porcine ventricular muscle2008

    • Author(s)
      Terui Y, Sodnomtseren M, Ishiwata S, Ohtsuki I, Fukuda N, Kurihara S
    • Organizer
      第31回心筋代謝研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-07-13
    • Related Report
      2009 Final Research Report
  • [Presentation] Thin filament-based regulation of length dependent activation in skinned porcine ventricular muscle.2008

    • Author(s)
      Terui Y, Sodnomtseren M*, Ishiwata S*, Ohtsuki I, Fukuda N, Kurihara S(*Department of Physics, Waseda University)
    • Organizer
      第31回心筋代謝研究会.
    • Place of Presentation
      東京
    • Year and Date
      2008-07-13
    • Related Report
      2008 Annual Research Report
  • [Presentation] Molecular basis for the Frank-Starli-ng mechanism of the heart2008

    • Author(s)
      Kurihara S, Fukuda N, Ohtsuki I, Terui T, Hongo K, Komukai K, Ishikawa T
    • Organizer
      心臓循環器系調節機構の病態生理学に関する国際シンポジウム
    • Place of Presentation
      山形
    • Year and Date
      2008-05-24
    • Related Report
      2009 Final Research Report
  • [Presentation] Molecular basis for the Frank-Starling mechanism of the heart.2008

    • Author(s)
      Kurihara S, Fukuda N, Ohtsuki I, Terui T, Hongo K, Komukai K, Ishikawa T
    • Organizer
      心臓循環器系調節機構の病態生理学に関する国際シンポジウム
    • Place of Presentation
      山形
    • Year and Date
      2008-05-24
    • Related Report
      2008 Annual Research Report
  • [Presentation] Decreased Ca2+ sensitivity of the myofilament is critcal for the development of cardiac dysfunction in mouse model of dilated cardiomyopathy2008

    • Author(s)
      Hongo K, (Kurihara S)
    • Organizer
      第72回日本循環器学会総会・学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2008-03-28
    • Related Report
      2009 Final Research Report
  • [Presentation] Decreased Ca^<2+> sensitivity of the myofilament is critcal for the d-evelopment of cardiac dysfunction in mouse model of dilated car-diomyopathy2008

    • Author(s)
      Hongo K
    • Organizer
      第72回日本循環器学会総会・学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2008-03-28
    • Related Report
      2007 Annual Research Report
  • [Presentation] Decreased Ca2+ affinity of thin filament is an important factor for the development of cardiac dysfunction in mouse model of dilated cardiomyopathy2008

    • Author(s)
      O-Uchi J, Hongo K, Morimoto S, Komukai K, Kawai M, Ohtsuki I, Morimoto S, Kurihara S
    • Organizer
      Thick and thin filament regulation in striated muscle
    • Place of Presentation
      Madison, USA
    • Related Report
      2009 Final Research Report
  • [Presentation] Microscopic analysis of sarcomeric oscillatioins by quantum dots in skinned rat ventricular myocytres2008

    • Author(s)
      Serizawa T, O-Uchi J, Fukuda N, Kurihara S, Ishiwata S
    • Organizer
      第46回日本生物物理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2009 Final Research Report
  • [Presentation] Decreased Ca^<2+>affinity of thin filament is an important factor for the development of cardiac dysfunction in mouse model of dilated cardiomyopathy.2008

    • Author(s)
      0-Uchi J, Hongo K, Morimoto s. Komukai K, Kawai M, Ohtsuki I, Morimoto S*, Kurihara S(*Laboratory of clinical pharmacology, Kyushu University graduate school of medicine)
    • Organizer
      Thick and thin filament regulation in striated muscle
    • Place of Presentation
      Madison, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Microscopic analysis of sarcomeric oscillatioins by quantum dots in skinned rat ventricular myocytres.2008

    • Author(s)
      Serizawa T^<1)>, 0-Uchi J, Fukuda N, Kurihara S, Ishiwata S^<l)2)>(^<l)>Graduate school of pure, applied physics, Waseda University, <1)2)>^Department of physics, school of science, engineering, Waseda University)
    • Organizer
      第46回日本生物物理学会年会.
    • Place of Presentation
      福岡
    • Related Report
      2008 Annual Research Report
  • [Presentation] Thin filament-based regulation of the Frank-Starling mechanism of the heart.2008

    • Author(s)
      Terui T, Ohtsuki I, Ishiwata S*, Fukuda N, Kurihara S(*Waseda University)
    • Organizer
      The 25^<th> annual meeting of the InternationalSociety for Heart Research Japanese Section.
    • Place of Presentation
      横浜
    • Related Report
      2008 Annual Research Report
  • [Presentation] Altered Ca2+ handling could contribute to the cardiac sudden death in knock-in mouse of dilated cardiomyopathy2007

    • Author(s)
      Hongo K, (Kurihara S)
    • Organizer
      第30回心筋代謝研究会
    • Place of Presentation
      京都
    • Year and Date
      2007-07-15
    • Related Report
      2009 Final Research Report
  • [Presentation] Altered Ca^<2+> handling could contribute to the cardiac sudden dea-th in knock-in mouse of dilated cardiomyopathy2007

    • Author(s)
      Hongo K
    • Organizer
      第30回心筋代謝研究会
    • Place of Presentation
      京都
    • Year and Date
      2007-07-15
    • Related Report
      2007 Annual Research Report
  • [Presentation] Changes in Ca2+ transient and contraction of left ventricular papillary muscles in mouse model of dilated cardiomyopathy2007

    • Author(s)
      Hongo K, (Kurihara S)
    • Organizer
      The 24th annual meeting of the International Society for Heart Research Japanese Section
    • Place of Presentation
      Ferrara, Italy
    • Year and Date
      2007-06-21
    • Related Report
      2009 Final Research Report
  • [Presentation] Changes in Ca^<2+> transient and contraction of left ventricular pap-illary muscles in mouse model of dilated cardiomyopathy2007

    • Author(s)
      Hongo K
    • Organizer
      The 24th annual meeting of the International Society for Heart Research Japanese Section
    • Place of Presentation
      Ferrara,Italy
    • Year and Date
      2007-06-21
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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