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Study on regulation mechanisms of cardiac rhythm and energy metabolism via mitochondria-sarcoplasmic reticulum coupling

Research Project

Project/Area Number 15H04674
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionUniversity of Fukui

Principal Investigator

Matsuoka Satoshi  福井大学, 学術研究院医学系部門, 教授 (00263096)

Co-Investigator(Kenkyū-buntansha) 竹内 綾子  福井大学, 学術研究院医学系部門, 准教授 (00378704)
Co-Investigator(Renkei-kenkyūsha) HIKIDA Masaki  秋田大学, 大学院理工学研究科, 教授 (60228715)
SHIMAYOSHI Takao  九州大学, 情報基盤研究開発センター, 准教授 (60373510)
Research Collaborator IINO Satoshi  福井大学, 学術研究院医学系部門, 教授 (40242854)
HORIGUCHI Kazuhide  福井大学, 学術研究院医学系部門, 准教授 (20377451)
FUKAZAWA Yugo  福井大学, 学術研究院医学系部門, 教授 (60343745)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsミトコンドリア / カルシウム / 心臓 / 数理モデル / 心臓生理 / トランスポータ / 心臓生理学 / モデル
Outline of Final Research Achievements

NCLX-knockout mice were created using the CRISPR-Cas9 method. Some of the homo-knockout mice show phenotypes different form wild type mice, such as low body weight, and abnormalities of heart and kidney. The Langendorff perfusion of mouse heart with a NCLX blocker (CGP-37157) tended to have decreased heart rate. In isolated mouse ventricular myocytes, CGP-37157 prolonged the 30 and 50% duration of action potential, and augmented the amplitude of Ca2+ transient probably due to the increase of SR Ca2+ content. A new comprehensive mathematical model of cardiac mitochondria was developed and published. A new mathematical model of sinoatrial cell, which contains the Ca2+ interaction between mitochondria and SR, was developed.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (29 results)

All 2018 2017 2016 2015 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (19 results) (of which Int'l Joint Research: 7 results,  Invited: 4 results) Remarks (4 results)

  • [Journal Article] Uncovering the arrhythmogenic potential of TRPM4 activation in atrial-derived HL-1 cells using novel recording and numerical approaches2017

    • Author(s)
      Hu Yaopeng、Duan Yubin、Takeuchi Ayako、Hai-Kurahara Lin、Ichikawa Jun、Hiraishi Keizo、Numata Tomohiro、Ohara Hiroki、Iribe Gentaro、Nakaya Michio、Mori Masayuki X.、Matsuoka Satoshi、Ma Genshan、Inoue Ryuji
    • Journal Title

      Cardiovascular Research

      Volume: 113 Issue: 10 Pages: 1243-1255

    • DOI

      10.1093/cvr/cvx117

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A simulation study on the constancy of cardiac energy metabolites during workload transition2016

    • Author(s)
      Saito R, Takeuchi A, Himeno Y, Inagaki N, Matsuoka S
    • Journal Title

      J Physiol

      Volume: 594 Issue: 23 Pages: 6929-6945

    • DOI

      10.1113/jp272598

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Patient-Specific Human Induced Pluripotent Stem Cell Model Assessed with Electrical Pacing Validates S107 as a Potential Therapeutic Agent for Catecholaminergic Polymorphic Ventricular Tachycardia2016

    • Author(s)
      Sasaki K, Makiyama T, Yoshida Y, Wuriyanghai Y, Kamakura T, Nishiuchi S, Hayano M, Harita T, Yamamoto Y, Kohjitani H, Hirose S, Chen J, Kawamura M, Ohno S, Itoh H, Takeuchi A, Matsuoka S, Miura M, Sumitomo N, Horie M, Yamanaka S, Kimura T
    • Journal Title

      PLoS One

      Volume: 11 Issue: 10 Pages: e0164795-e0164795

    • DOI

      10.1371/journal.pone.0164795

    • NAID

      120005860036

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysregulation of a potassium channel, THIK-1, targeted by caspase-8 accelerates cell shrinkage2016

    • Author(s)
      Sakamaki K, Ishii TM, Sakata T, Takemoto K, Takagi C, Takeuchi A, Morishita R, Takahashi H, Nozawa A, Shinoda H, Chiba K, Sugimoto H, Saito A, Tamate S, Satou Y, Jung SK, Matsuoka S, Koyamada K, Sawasaki T, Nagai T, Ueno N
    • Journal Title

      Biochim Biophys Acta

      Volume: 1863 Issue: 11 Pages: 2766-2783

    • DOI

      10.1016/j.bbamcr.2016.08.010

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of the mitochondrial Na+-Ca2+ exchanger, NCLX, in B lymphocyte chemotaxis2016

    • Author(s)
      Kim B, Takeuchi A, Hikida M, Matsuoka S
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 28378-28378

    • DOI

      10.1038/srep28378

    • NAID

      120006349330

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The ventromedial hypothalamus oxytocin induces locomotor behavior regulated by estrogen2016

    • Author(s)
      Narita K, Murata T, Matsuoka S
    • Journal Title

      Physiol Behav

      Volume: 9384 Pages: 30297-9

    • DOI

      10.1016/j.physbeh.2016.05.047

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Intracellular localization of mitochondrial Na+-Ca2+ exchanger NCLX in mice ventricular myocytes.2018

    • Author(s)
      Satoshi Matsuoka, Ayako Takeuchi
    • Organizer
      Biophysical Society 62th Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A simulation study on Ca2+ regulation of energy metabolism in cardiac mitochondria2017

    • Author(s)
      Satoshi Matsuoka, Ayako Takeuchi, Ryuta Saito, Yukiko Himeno
    • Organizer
      The 94th Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      ACT CITY (Shizuoka, Hamamatsu)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Physiome study on the roles of mitochondria-endoplasmic reticulum Ca2+ crosstalk in lymphocytes2017

    • Author(s)
      Ayako Takeuchi, Bongju Kim, Satoshi Matsuoka
    • Organizer
      The 94th Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      ACT CITY (Shizuoka, Hamamatsu)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Mechanisms for external K+ dependence of K+ permeation and gating of Kir2.1 inward rectifier K+ channel2017

    • Author(s)
      Keiko Ishihara, Satoshi Matsuoka, Makoto Takano
    • Organizer
      The 94th Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      ACT CITY (Shizuoka, Hamamatsu)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] A theoretical study on the roles of Ca2+ in the energy metabolite stability during cardiac workload transition2017

    • Author(s)
      Ayako Takeuchi, Ryuta Saito, Yukiko Himeno. Satoshi Matsuoka
    • Organizer
      Biophysical Society 61th Annual Meeting
    • Place of Presentation
      New Orleans (USA)
    • Year and Date
      2017-02-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Frequency-dependences of action potential and Ca2+ transient and roles of mitochondrial Na+/Ca2+ exchange in mice ventricular myocytes.2017

    • Author(s)
      Yukari Takeda, Misaki Tsukioka, Shino Fujisawa, Moe Fujisawa, Yousuke Shimizu, Erika Iwai, Rena Horie, Saki Matsunaka, Ayako Takeuch, Satoshi Matsuoka
    • Organizer
      Cardiac Physiome Society's 20th Workshop
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Na/Ca exchange and Mitochondria function -The use of Mathematical models-2017

    • Author(s)
      Satoshi Matsuoka
    • Organizer
      IUPS 38th world congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 心臓仕事量増大時におけるエネルギー代謝産物安定性制御メカニズムに関する数理解析2016

    • Author(s)
      竹内綾子、齋藤隆太、姫野友紀子、松岡達
    • Organizer
      第63回 中部日本生理学会
    • Place of Presentation
      岡崎カンファレンスセンター(愛知県・岡崎市)
    • Year and Date
      2016-11-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 新規ミトコンドリアエネルギー代謝数理モデルを用いた心臓エネルギー代謝制御メカニズムの解析2016

    • Author(s)
      竹内綾子、齋藤隆太、姫野友紀子、松岡達
    • Organizer
      生理学研究所 研究会「心臓・血管系の包括的な機能統合研究」
    • Place of Presentation
      九州大学(福岡県・福岡市)
    • Year and Date
      2016-10-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 細胞内カルシウム濃度かミトコントリアエネルギー代謝に与える影響のシミュレーション解析2016

    • Author(s)
      西村優汰, 嶋吉隆夫, 竹内綾子, 松田哲也, 松岡達
    • Organizer
      生体医工学シンポジウム
    • Place of Presentation
      大雪クリスタルホール国際会議場(北海道・旭川)
    • Year and Date
      2016-09-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] A simulation study on roles of Ca2+ in constancy of cardiac energy metabolites during workload transition2016

    • Author(s)
      Ayako Takeuchi, Ryuta Saito, Yukiko Himeno, Satoshi Matsuoka
    • Organizer
      2016 Cardiac Physiome Workshop
    • Place of Presentation
      Seoul (Republic of Korea)
    • Year and Date
      2016-08-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Simulation of Cellular Responses to Myocardial Anoxia and Acidosis2016

    • Author(s)
      Yuta Nishimura, Takao Shimayoshi, Ayako Takeuchi, Tetsuya Matsuda, and Satoshi Matsuoka
    • Organizer
      38th Annual International Conference of the IEEE Engineering in Medicine & Biology Society
    • Place of Presentation
      Orland (USA)
    • Year and Date
      2016-08-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ミトコンドリア-筋小胞体構造的クロストークを考慮したマウス洞房結節細胞数理モデルの構築2016

    • Author(s)
      竹内綾子, 松岡達
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] 心臓リズム・代謝制御機構2016

    • Author(s)
      松岡 達
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリア-小胞体Ca2+クロストークに関するフィジオーム研究2016

    • Author(s)
      竹内綾子, 松岡達
    • Organizer
      日本膜学会第38年会
    • Place of Presentation
      早稲田大学(東京)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 心筋細胞 HL -1の周期的 Ca transient発生におけるvitamin D receptorの関与2015

    • Author(s)
      村田 拓也、竹内 綾子、松岡 達
    • Organizer
      生理学研究所研究会 「心臓・血管系の包括的な機能統合研究」
    • Place of Presentation
      生理学研究所 岡崎
    • Year and Date
      2015-10-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] Physiome study on mitochondrial Ca2+ dynamics.2015

    • Author(s)
      Satoshi Matsuoka and Ayako Takeuchi.
    • Organizer
      67th Annual meeting of the Korean Physiological Society.
    • Place of Presentation
      韓国 プサン
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Contribution of mitochondria to the generation of automaticity of sinoatrial node cells; a simulation study2015

    • Author(s)
      Takeuchi A, Horiguchi K, Iino S, Fukazawa Y, Matsuoka S.
    • Organizer
      e-Heartシンポジウム
    • Place of Presentation
      立命館大学 南草津
    • Year and Date
      2015-09-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] Simulation analysis of automaticity of sinoatrial node myocytes2015

    • Author(s)
      Ayako Takeuchi, Satoshi Matsuoka
    • Organizer
      Society for Mathematical Biology 2015 conference
    • Place of Presentation
      米国 アトランタ
    • Year and Date
      2015-06-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 福井大学医学部統合生理学ホームページ

    • URL

      http://seiri2.med.lab.u-fukui.ac.jp/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 福井大学医学部統合生理学ホームページ(英語)

    • URL

      http://isphysio.med.u-fukui.ac.jp/

    • Related Report
      2016 Annual Research Report
  • [Remarks]

    • URL

      http://seiri2.med.lab.u-fukui.ac.jp/

    • Related Report
      2015 Annual Research Report
  • [Remarks]

    • URL

      http://isphysio.med.u-fukui.ac.jp/

    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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