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Coordination and dissociation of nonlinear oscillations in cardiomyocytes : dysfunction of holonic oscillators leading to arrhythmias

Research Project

Project/Area Number 19300153
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionHokkaido University

Principal Investigator

KAWAHARA Koichi  Hokkaido University, 大学院・情報科学研究科, 教授 (20125397)

Co-Investigator(Kenkyū-buntansha) OKU Yoshitaka  兵庫医科大学, 医学部, 教授 (20252512)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2008: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2007: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Keywords心筋細胞 / 細胞内Ca^<2+>振動 / ATP-purinoceptor系 / 細胞外ATP振動 / 細胞内Mg^<2+>振動 / 非線形振動子 / 負帰還制御系 / ATP-purinocetor系
Research Abstract

We have recently found that the extracellular ATP-purinoceptor signaling is crucially involved in the intercellular synchronization of intracellular Ca^<2+> oscillations among cardiomyocytes. In this study, I aim at elucidating whether and how the concentrations of extracellular ATP and intracellular Mg^<2+> oscillate in association with rhythmic contraction of cultured cardiomyocytes from neonatal rats. The simultaneous measurement of the fluo-4 fluorescence and the luciferin/luciferase chemical luminescence showed that the concentration of extracellular ATP oscillated synchronously with the concentration of intracellular Ca^<2+> in cardiomyocytes, supporting our previous inference that the extracellular ATP-purinoceptor signaling is responsible for the intercellular synchronization of intracellular Ca^<2+> oscillations. In addition, the concentration of intracellular Mg^<2+> also oscillated in association with rhythmic contraction and intracellular Ca^<2+> oscillations, suggesting that the concentration of intracellular ATP varied depending on the rhythmic contraction of cardiomyocytes. All these findings have led to an idea that the coordination of multiple nonlinear oscillations in cardiomyocytes such as rhythmic variations in the concentrations of intracellular Ca^<2+> Mg^<2+> and ATP seems critical to the normal function of the heart.

Report

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

    (42 results)

All 2009 2008 2007 Other

All Journal Article (28 results) (of which Peer Reviewed: 26 results) Presentation (10 results) Remarks (4 results)

  • [Journal Article] Proliferation of neonatal cardiomyocytes by connexin43 knockdown via synergistic inactivation of p38 MAPK and increased expression of FGF12009

    • Author(s)
      Matsuyama, D., Kawahara, K.
    • Journal Title

      Basic Research in Cardiology 104(6)

      Pages: 631-642

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Power-Law stress and creep relaxations of single cells measured by colloidal probe atomic force microscopy2009

    • Author(s)
      Hiratsuka, S., Mizutani, Y., Toda, A., Fukushima, N., Kawahara, K., Tokumoto, H., Okajima. T.
    • Journal Title

      Japanese Journal of Applied Physics 48

    • NAID

      210000067323

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of extracellular ATP-P2Y purinoceptor signaling in ischemia-induced tolerance of astrocytes in culture2009

    • Author(s)
      Iwabuchi, S., Kawahara, K.
    • Journal Title

      Neurochemical Research 34(9)

      Pages: 1542-1554

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The number distribution of complex shear modulus of single cells measured by atomic force microscopy2009

    • Author(s)
      Hiratsuka, S., Mizutani, Y., Tsuchiya, M., Kawahara, K., Tokumoto, H., Okajima, T.
    • Journal Title

      Ultramicroscopy 109

      Pages: 937-941

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oxygen-glucose deprivation-induced enhancement of extracellular ATP-P2Y purinoceptors signaling for the propagation of astrocytic calcium waves2009

    • Author(s)
      Iwabuchi, S., Kawahara, K.
    • Journal Title

      BioSystems 96

      Pages: 35-43

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] 互いに孤立した心筋細胞の同期現象 : 細胞間情報伝達の新しいメカニズム2009

    • Author(s)
      河原剛一
    • Journal Title

      心電図 29 Suppl. 5

    • NAID

      10026293308

    • Related Report
      2009 Final Research Report
  • [Journal Article] Oxygen-glucose deprivation-induced enhancement of extracellular ATP-P2Y purinoceptors signaling for the propagation of astrocytic calcium waves.2009

    • Author(s)
      Iwabuchi, S.
    • Journal Title

      BioSystoms 96

      Pages: 35-43

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The number distribution of complex shear modulus of single cells measured by atomic force microscopy.2009

    • Author(s)
      Hiratsuka, S.
    • Journal Title

      Ultramicroscopy 109

      Pages: 937-941

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of extracellular ATP-P2Y purinoceptor signaling in ischemia-induced tolerance of astrocytes in culture.2009

    • Author(s)
      Iwabichi, S.
    • Journal Title

      Neurochemical Research 34

      Pages: 1542-1554

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rhythmic fluctuations in the concentration of intracellular Mg^<2+> in association with spontaneous rhythmic contraction in cultured cardiac myocytes2008

    • Author(s)
      Kawahara, K., Sato, R., Iwabuchi, S., Matsuyama, D.
    • Journal Title

      Chronobiology International 25(6)

      Pages: 868-881

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Elasticity of living cells on a microarray during the early stages of adhesion measured by atomic force microscopy2008

    • Author(s)
      Mizutani, Y., Tsuchia, M., Hiratsuka, S., Kawahara, K., Tokumoto, H., Okajima, T.
    • Journal Title

      Japanese Journal of Applied Physics 47(7)

      Pages: 6177-6180

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Maintenance and characterization of spontaneous contraction rhythm in cultured cardiac myocytes fused with cardiac fibroblasts2008

    • Author(s)
      Matsuyama, D., Kawahara, K.
    • Journal Title

      BioSystems 92

      Pages: 226-232

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neuron is the primary target of Ca^<2+> paradox-type insult-induced cell injury in neuron/astrocyte co-cultures2008

    • Author(s)
      Kosugi, T., Kawahara, K., Tanaka, M., Watanabe, Y., Inanami, O.
    • Journal Title

      Neurochemistry International 52(4-5)

      Pages: 887-896

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Changes in the Proliferation activity and spontaneous contraction rhythm of terminally differentiated cardiac myocytes by co-treatment with FGF1 and an inhibitor of p38 MAP Kinase2008

    • Author(s)
      Matsuyama, D., Kawahara, K.
    • Journal Title

      The 22nd SICE Symposium on Biological and Physiological Engineering, Harbin, China, January 13-14, 2008. (Proceedings of the International Symposium on Biological and Physiological Engineering)

      Pages: 337-338

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rhythmic fluctuations in intracellular Mg2+ in spontaneously beating cultured cardiac myocytes2008

    • Author(s)
      Kawahara, K., Sato, R., Matsuyama, D., Iwabuchi, S
    • Journal Title

      Proceedings of the NBC 2008

      Pages: 264-267

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neuron is the primary target of Ca^<2+> paradox-type insult-induced cell injury in neuron / astrocyte co-cultures2008

    • Author(s)
      Tatsuro Kosugi
    • Journal Title

      Neurochemistry International 52

      Pages: 887-896

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maintenance and characterization of spontaneous contraction rhythm in cultured cardiac myocytes fused withcardiac fibroblasts2008

    • Author(s)
      Daisuke Matsuyama
    • Journal Title

      BioSystems 92

      Pages: 226-232

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rhythmic fluctuations in the concentration of intracellular Mg^<2+> in association with spontaneous, rhythmic contraction in cultured cardiac myocytes2008

    • Author(s)
      Koichi Kawahara
    • Journal Title

      Chronobiology International 25

      Pages: 868-881

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluctuations in the concentration of extracellular ATP synchronized with intracellular Ca2+ oscillatory rhythm in cultured cardiac myocytes2007

    • Author(s)
      Kawahara, K., Nakayama, Y.
    • Journal Title

      Chronobiology International 24(6)

      Pages: 1035-1048

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Changes in the fluctuation of the contraction rhythm of spontaneously beating cardiac myocytes in cultures with and without cardiac fibroblasts2007

    • Author(s)
      Hachiro, T., Kawahara, K., Sato, R., Yamauchi, Y., Matsuyama, D.
    • Journal Title

      BioSystems 90

      Pages: 707-715

    • NAID

      120000951583

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preconditioning-induced changes in the spontaneous calcium oscillations for the development of neuronal ischemic tolerance in neuron/astrocyte co-culture2007

    • Author(s)
      Tanaka, M., Kawahara, K., Kosugi, T., Yamada, T., Mioka, T.
    • Journal Title

      Neurochemical Research 32

      Pages: 988-1001

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of ATP-purinoceptor signaling in the intercellular synchronization of intracellular Ca2+ oscillation in cultured cardiac myocytes2007

    • Author(s)
      Nakayama, Y., Kawahara, K., Hachiro, T., Yamauchi, Y., Yoneyama, M.
    • Journal Title

      BioSystems 90

      Pages: 179-187

    • NAID

      120000966384

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Extracellular ATP-purinoceptor signaling for the intercellular synchronization of intracellular calcium oscillation in cultured cardiac myocytes2007

    • Author(s)
      Kawahara, K., Nakayama, Y.
    • Journal Title

      IFMBE Proceedings Volume 16

      Pages: 537-540

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of nitric oxide in the suppression of the release of cellular ATP during ischemia in cultured cardiac myocytes2007

    • Author(s)
      Kawahara, K., Hachiro, T., Matsuyama, D.
    • Journal Title

      New Horizons in Coronary Artery Disease

      Pages: 79-82

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] 心筋細胞内Ca2+振動の細胞間同期と自動能 : その新しいメカニズム2007

    • Author(s)
      河原剛一
    • Journal Title

      臨床と研究 84(3)

      Pages: 441-444

    • Related Report
      2009 Final Research Report
  • [Journal Article] Fluctuations in the concentration of extracellular ATP synchronized with intracellular Ca^<2+> oscillatory rhythm in cultured cardiac myocytes2007

    • Author(s)
      Koichi Kawahara
    • Journal Title

      Chronobiology International 24

      Pages: 1035-1048

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes in the fluctuation of the contraction rhythm of spontaneously beating cardiac myocytes in cultures with and without cardiac fibroblasts2007

    • Author(s)
      Takeru Hachiro
    • Journal Title

      BioSystems 90

      Pages: 707-715

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of ATP-purinoceptor signaling in the intercellular synchronization of intracellular Ca^<2+> oscillation in cultured cardiac myocytes2007

    • Author(s)
      Yukako Nakayama
    • Journal Title

      BioSystems 90

      Pages: 179-187

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Development of a new in vitro model of Brain Ischemia by focal photolysis of a caged glutamate in neuron and glia cocultures.2009

    • Author(s)
      Iwabuchi, S.
    • Organizer
      XXXVI International Congress of Physiological Sciences
    • Place of Presentation
      Kyoto International Conference Center, Kyoto, Japan
    • Year and Date
      2009-07-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] Sublethal ischaemia enhances the expression of glucose transporter 3 in cultured astrocytes2009

    • Author(s)
      Iwabuchi, S., Kawahara, K.
    • Organizer
      19th Annual Meeting of the European Neurological Society
    • Place of Presentation
      Milano
    • Related Report
      2009 Final Research Report
  • [Presentation] 低出力超音波パルス刺激が線維芽細胞遊走能に与える影響について2009

    • Author(s)
      岩淵禎弘, 松山大輔, 河原剛一
    • Organizer
      第48回日本生体医工学会大会
    • Related Report
      2009 Final Research Report
  • [Presentation] 互いに孤立した心筋細胞の同期現象 : 細胞間情報伝達の新しいメカニズム2008

    • Author(s)
      河原剛一
    • Organizer
      第23回犬山不整脈カンファレンス
    • Place of Presentation
      福岡
    • Year and Date
      2008-08-30
    • Related Report
      2009 Final Research Report
  • [Presentation] Rhythmic fluctuations in intracellular Mg^<2+> in spontaneously beating cultured cardiac myocytes2008

    • Author(s)
      Koichi Kawahara
    • Organizer
      14^<th> Nordic-Baltic Conference on Biomedical Engineering and Medical Physics (NBC 2008)
    • Place of Presentation
      Reval Hotel Latvia, Riga (Latvia)
    • Year and Date
      2008-06-19
    • Related Report
      2008 Annual Research Report
  • [Presentation] Elasticity of Cardiac Cells on a Microarray under Oxidative Stress Measured by Atomic Force Microscopy. Y. Mizutani, M. Tsuchiya, S. Hiratsuka, K. Kawahara, H. Tokumoto, and T. Okajima2008

    • Author(s)
      Mizutani, Y., Tsuchiya, M., Hiratsuka, S., Kawahara, K., Tokumoto, H., Okajima, T.
    • Organizer
      International Scanning Probe Microscopy Conference Seattle '08, Seattle, WA, U.S.A.
    • Place of Presentation
      International Scanning Probe Microscopy Conference Seattle Meeting program
    • Related Report
      2009 Final Research Report
  • [Presentation] 虚血・再灌流によるグリア細胞間カルシウム情報伝達機構の変化2008

    • Author(s)
      岩淵禎弘, 河原剛一
    • Organizer
      第47回生体医工学会大会
    • Place of Presentation
      生体医工学
    • Related Report
      2009 Final Research Report
  • [Presentation] Extracellular ATP-purinoceptor signaling for the intercellular synchronization of intracellular calcium oscillation in cultured cardiac myocytes2007

    • Author(s)
      Koichi Kawahara
    • Organizer
      MEDICON 2007
    • Place of Presentation
      University of Ljubljana, Ljubljana (Slovenia)
    • Year and Date
      2007-06-28
    • Related Report
      2007 Annual Research Report
  • [Presentation] Force measurements of microarray living cells2007

    • Author(s)
      Mizutani, Y., Tsuchiya, M., Hiratsuka, S., Kawahara, K., Tokumoto, H., Okajima, T.
    • Organizer
      Proceedings of the 15^<th> International Colloquium on Scanning Probe Microscopy (ICSPM15)
    • Place of Presentation
      Atagawa, Japan
    • Related Report
      2009 Final Research Report
  • [Presentation] 異種細胞融合による終末分化心筋細胞・細胞周期リエントリーの可能性2007

    • Author(s)
      松山大輔, 河原剛一
    • Organizer
      生体医工学
    • Place of Presentation
      第46回生体医工学会大会, 仙台
    • Related Report
      2009 Final Research Report
  • [Remarks] ホームページ等

    • URL

      http://cell-c.ist.hokudai.ac.jp/

    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

      http://cell-c.ist.hokudai.ac.jp/

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://cell-c.ist.hokudai.ac.jp/

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://cell-c.ist.hokudai.ac.jp/

    • Related Report
      2007 Annual Research Report

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

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