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In vivo nano-analysis of cardiac excitation-contraction coupling.

Research Project

Project/Area Number 18K06878
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionJikei University School of Medicine

Principal Investigator

Kobirumaki-Shimozawa Fuyu  東京慈恵会医科大学, 医学部, 助教 (40548905)

Co-Investigator(Kenkyū-buntansha) 照井 貴子  東京慈恵会医科大学, 医学部, 講師 (10366247)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsサルコメア / in vivoイメージング / 心筋 / ナノ計測 / サルコメア長 / 興奮収縮連関 / 動態解析 / Ca2+ / 活動電位 / サルコメア動態 / 心筋細胞内カルシウム動態 / 心筋細胞
Outline of Final Research Achievements

Using our proprietary in vivo confocal microscopy system with high spatial and temporal resolution, we have succeeded in elucidating one aspect of the hierarchical principle of cardiac beating by extracting molecular information on the contractile apparatus in cardiomyocytes, specifically the sarcomere length in beating myocytes of living mice. By measuring sarcomere lengths at the nanometer scale, they found that individual sarcomere lengths in myofibrils varied, with a mixture of sarcomeres that were tuned to myofiber contraction and sarcomeres that were not. By using nano-measurements, they discovered for the first time in the world that sarcomere entrainment regulates myocardial contractility, and published a paper on their findings (Kobirumaki-Shimozawa et al., 2021).

Academic Significance and Societal Importance of the Research Achievements

本研究では、マウスin vivo心臓の各部位から心筋細胞内の分子情報(サルコメア長等)を、ナノメーター・ミリ秒スケールで解析してin vivoにおけるサルコメア同調性の変調をナノスケールで明らかにすることにより、正常および抑圧状態の心臓を生理学的分子論に基づいて定量化・明確化することに成功した。この成果を心疾患に応用し、各心疾患におけるin vivo興奮収縮連関の変化をナノスケールで定量化することができれば、心筋症発症の分子メカニズムの解明とそれに続く心臓のマクロ機能を正常化させる治療法の開発などに貢献し、将来的には心疾患の死亡率を劇的に低下させる「心臓ナノ医学」の創成につながると期待される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2022 2021 2020 2019 2018 Other

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

  • [Int'l Joint Research] Oslo University Hospital/University of Oslo(ノルウェー)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Oslo University Hospital/University of Oslo(ノルウェー)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Synchrony of sarcomeric movement regulates left ventricular pump function in the in vivo beating mouse heart.2021

    • Author(s)
      Fuyu Kobirumaki-Shimozawa, Togo Shimozawa, Kotaro Oyama, Shunsuke Baba, Jia Li, Tomohiro Nakanishi, Takako Terui, William Louch, Shin'ichi Ishiwata, and Norio Fukuda.
    • Journal Title

      The Journal of General Physiology

      Volume: 153 Issue: 11

    • DOI

      10.1085/jgp.202012860

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Thermal activation of thin filaments in striated muscle2020

    • Author(s)
      Shuya Ishii, Kotaro Oyama, Seine A. Shintani, Fuyu Kobirumaki-Shimozawa, Shin'Ichi Ishiwata, Norio Fukuda.
    • Journal Title

      Frontiers in Physiology, section Striated Muscle Physiology

      Volume: 11 Pages: 278-278

    • DOI

      10.3389/fphys.2020.00278

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real-Time In Vivo Imaging of Mouse Left Ventricle Reveals Fluctuating Movements of the Intercalated Discs2020

    • Author(s)
      Kobirumaki-Shimozawa Fuyu、Nakanishi Tomohiro、Shimozawa Togo、Terui Takako、Oyama Kotaro、Li Jia、Louch William E.、Ishiwata Shin’ichi、Fukuda Norio
    • Journal Title

      Nanomaterials

      Volume: 10 Issue: 3 Pages: 532-532

    • DOI

      10.3390/nano10030532

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Microscopic heat pulses activate cardiac thin filaments2019

    • Author(s)
      Ishii Shuya、Oyama Kotaro、Arai Tomomi、Itoh Hideki、Shintani Seine A.、Suzuki Madoka、Kobirumaki-Shimozawa Fuyu、Terui Takako、Fukuda Norio、Ishiwata Shin'ichi
    • Journal Title

      Journal of General Physiology

      Volume: 151 Issue: 6 Pages: 860-869

    • DOI

      10.1085/jgp.201812243

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo心臓ナノイメージング法の開発2019

    • Author(s)
      下澤東吾、小比類巻生、大山廣太郎、照井貴子、福田紀男
    • Journal Title

      生物物理

      Volume: 59 Pages: 009-013

    • NAID

      130007557818

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Optimization of Fluorescent Labeling for In Vivo Nanoimaging of Sarcomeres in the Mouse Heart2018

    • Author(s)
      Kobirumaki-Shimozawa Fuyu、Shimozawa Togo、Oyama Kotaro、Kushida Yasuharu、Terui Takako、Ishiwata Shin’ichi、Fukuda Norio
    • Journal Title

      BioMed Research International

      Volume: 2018 Pages: 1-8

    • DOI

      10.1155/2018/4349170

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sarcomeric Auto-Oscillations in Single Myofibrils From the Heart of Patients With Dilated Cardiomyopathy2018

    • Author(s)
      Kagemoto Tatsuya、Oyama Kotaro、Yamane Mitsunori、Tsukamoto Seiichi、Kobirumaki-Shimozawa Fuyu、Li Amy、Dos Remedios Cristobal、Fukuda Norio、Ishiwata Shin’ichi
    • Journal Title

      Circulation: Heart Failure

      Volume: 11 Issue: 7

    • DOI

      10.1161/circheartfailure.117.004333

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] In vivo心臓ナノ生理学: サルコメア運動の同調性によるポンプ機能の制御2022

    • Author(s)
      小比類巻 生
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] サルコメア運動の同調性によるマウス左心室ポンプ機能の制御2021

    • Author(s)
      小比類巻 生, 下澤 東吾, 大山 廣太郎, Li Jia, 中西 智博, 照井 貴子, Louch William E., 石渡 信一, 福田 紀男
    • Organizer
      第98回日本生理学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] In vivoナノイメージングによる心筋サルコメアの動態解析2019

    • Author(s)
      小比類巻生、下澤東吾、Li Jia、Louch William E.、石渡信一、福田紀男
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] In vivo nano-analysis of the dynamics of individual sarcomeres in the beating mouse heart.2019

    • Author(s)
      Fuyu Kobirumaki-Shimozawa, Kotaro Oyama, Togo Shimozawa, Shin’ichi Ishiwata, Norio Fukuda
    • Organizer
      9th Federation of the Asian and Oceanian Pysiological Societies congress in conjunction with The 96th Annual Meeting of the Physiological Society of Japan
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Microscopic heat pulses induce activation od cardiac thin filaments in the in vitro motility assay.2019

    • Author(s)
      Shuya-Ishii, Kotaro Oyama, Tomomi Arai, Hideki Itoh, Seine A. Shintani, Madoka Suzuki, Fuyu Kobirumaki-Shimozawa, Shin’ichi Ishiwata, Norio Fukuda
    • Organizer
      9th Federation of the Asian and Oceanian Pysiological Societies congress in conjunction with The 96th Annual Meeting of the Physiological Society of Japan
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] In vivoマウス心筋における単一サルコメア動態のイメージング2018

    • Author(s)
      小比類巻生, 下澤東吾, 大山廣太郎, 石渡信一, 福田紀男
    • Organizer
      第56回日本生物物理学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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