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Role of Microtubules in the Muscle Structure-Contraction Relationship

Research Project

Project/Area Number 20K11368
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59020:Sports sciences-related
Research InstitutionJuntendo University

Principal Investigator

Kobayashi Takuya  順天堂大学, 医学部, 助教 (60468585)

Co-Investigator(Kenkyū-buntansha) 茅 元司  東京大学, 大学院理学系研究科(理学部), 助教 (00422098)
渡邊 大輝  広島大学, 人間社会科学研究科(総), 助教 (30823281)
呉林 なごみ  順天堂大学, 医学部, 客員准教授 (50133335)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords骨格筋 / 微小管 / 粘弾性 / 衝撃耐性 / イメージング / 筋収縮 / 筋挫傷
Outline of Research at the Start

骨格筋はその特異な筋構造に由来する収縮力を発揮する事で、運動器としての役割を果たしている。さらに、体外からの外力に抗して身体を防御している。骨格筋は身体にとって力強い器官であるが、常に損傷の危険に晒されているため、筋構造の力学的安定性は筋機能に必須である。「筋構造―収縮力相関」の構成要素はかなりの範囲で分かってきているが、微小管の「筋構造―収縮力相関」への寄与はほとんどわかっていない。本研究では骨格筋に負荷を与えながら、そこに微小管作用薬を投与し、収縮力計測と筋構造イメージングを組み合わせることで「筋構造―収縮力相関」における微小管の寄与を定量的に解明することを目的とする。

Outline of Final Research Achievements

The purpose of this study was to clarify the role of microtubules in the contractile function of skeletal muscle. For this purpose, we developed a device for simultaneous measurement of tension and muscle imaging. A stepping motor for external force strain was incorporated and a movable microscope was constructed to realize highly accurate measurement of contraction force and deformation stress with low noise. By examining the excitation light wavelength and excitation light illumination method for imaging, optical damage and background light noise during repetitive contraction and extension deformation were greatly reduced, and tension force measurement was successfully performed while visualizing the inside of muscle fibers. Using this system, it was also clarified that microtubules are related to the strength of tetanus contraction and deformation stress relaxation time of skeletal muscle.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は張力計測とイメージングの同時計測法の確立および微小管の骨格筋粘弾性への寄与の解明という二つの点である。前者は異なる計測方法を同一時間軸で行うための技術開発である。近年の生命科学研究においては、生物システムの多要素的理解や分子・細胞・個体間の階層横断的理解が求められているが、生きた筋組織の多元的計測はその両者に貢献するものである。また、骨格筋粘弾性における微小管の寄与を示した事は骨格筋研究に新たな視点を提供することになった。これは筋の衝撃耐性や運動性能の理解に繋がるため、トレーニング法、マッサージ療法やスポーツウェア開発などの身体運動諸分野に波及するものである。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (9 results)

All 2023 2022 2021

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Novel Calmodulin Variant p.E46K Associated With Severe Catecholaminergic Polymorphic Ventricular Tachycardia Produces Robust Arrhythmogenicity in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.2023

    • Author(s)
      Gao J, Makiyama T, Yamamoto Y, Kobayashi T, Aoki H, Maurissen TL, Wuriyanghai Y, Kashiwa A, Imamura T, Aizawa T, Huang H, Kohjitani H, Nishikawa M, Chonabayashi K, Fukuyama M, Manabe H, Nakau K, Wada T, Kato K, Toyoda F, Yoshida Y, Makita N, Woltjen K, Ohno S, Kurebayashi N, Murayama T, Sakurai T, Horie M, Kimura T.
    • Journal Title

      Circulation: Arrhythmia and Electrophysiology

      Volume: 16 Issue: 3 Pages: 9999-9999

    • DOI

      10.1161/circep.122.011387

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Therapeutic effects of novel type1 ryanodine receptor inhibitor on skeletal muscle diseases2022

    • Author(s)
      Yamazawa Toshiko、Kobayashi Takuya、Kurebayashi Nagomi、Murayama Takashi
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 157 Issue: 1 Pages: 15-22

    • DOI

      10.1254/fpj.21068

    • NAID

      130008138777

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel RyR1-selective inhibitor prevents and rescues sudden death in mouse models of malignant hyperthermia and heat stroke2021

    • Author(s)
      Yamazawa Toshiko、Kobayashi Takuya、Kurebayashi Nagomi、Konishi Masato、Noguchi Satoru、Inoue Takayoshi、Inoue Yukiko U.、et al.
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 4293-4293

    • DOI

      10.1038/s41467-021-24644-1

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Ryanodine Receptor as a Sensor for Intracellular Environments in Muscles2021

    • Author(s)
      Kobayashi Takuya、Kurebayashi Nagomi、Murayama Takashi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 19 Pages: 10795-10795

    • DOI

      10.3390/ijms221910795

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The effects of microtubule depolymerization on muscular viscoelastic properties.2023

    • Author(s)
      T Kobayashi, N Kurebayashi, Murayama, T Sakurai, M Kaya
    • Organizer
      The 5th Rocky Mountain Muscle Symposium
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨格筋の粘弾性における微小管の役割2023

    • Author(s)
      小林 琢也, 茅 元司,呉林 なごみ, 村山 尚, 櫻井 隆
    • Organizer
      第61回日本生物物理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 骨格筋のしなやかさ~粘弾性に寄与する微小管~2023

    • Author(s)
      小林 琢也
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 微小管脱重合薬により骨格筋の粘弾性は変化する2022

    • Author(s)
      小林 琢也, 村山 尚, 呉林 なごみ
    • Organizer
      第60回日本生物物理学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] 発熱する骨格筋、イオンチャネルの暴走2022

    • Author(s)
      小林琢也
    • Organizer
      第11回分子モーター討論会
    • Related Report
      2022 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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