High-precision analysis of myocardial contraction mechanism in rat isolated perfused heart.

• Project/Area Number: 16K18993
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Terui Takako 東京慈恵会医科大学, 医学部, 講師 (10366247)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 循環生理 / 循環生理学 / 生理学 / 生物物理

Outline of Final Research Achievements

Numerous studies have been conducted in isolated tissues and cells to elucidate the molecular mechanisms of myocardial contraction. However, our knowledge is still limited on the dynamics of myocardial sarcomere contraction in the heart of living animals. In the present study, we developed a novel system enabling us to conduct the imaging of a single sarcomere in the rat isolated perfused heart. We expressed GFP at Z-disks (α-actinin-GFP) in the heart by using the adenovirus vector system, and conducted imaging of the movement of a single sarcomere. In order to estimate the magnitude of regional myocardial movement, we imaged voltage-sensitive dye on the beating isolated heart. We successfully observed striations along cardiomyocytes in the isolated perfused heart. Moreover, we generated the ex-vivo imaging system with two different images of an object through a single video camera.

Academic Significance and Societal Importance of the Research Achievements

生命科学・医学研究において生体内の様々な制御メカニズムを解明するためには、in vitro のみならずin vivoでの分子メカニズムの解明が待たれるが、心筋研究においては、心臓自体が常に拍動し続けている臓器であるため、その技術的な難しさからin vivo研究はほとんど行われていない。in-vitroからin-vivoイメージングへ研究を進めていく上で、非常に重要なex-vivoイメージング装置を開発し、本研究をより実質的かつ装置系に段階性を持たせて進められ、ex-vivoイメージング装置を実際に使用し、擬似生体内での心筋サルコメアの収縮・弛緩動態を解明できる装置系と考えられる。

Research Products

• [Journal Article] Real-Time In Vivo Imaging of Mouse Left Ventricle Reveals Fluctuating Movements of the Intercalated Discs (2020)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Microscopic heat pulses activate cardiac thin filaments (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Optimization of Fluorescent Labeling for In Vivo Nanoimaging of Sarcomeres in the Mouse Heart (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] In vivo cardiac nano-imaging: A new technology for high-precision analyses of sarcomere dynamics in the heart (2017)
  • Author(s): Togo Shimozawa, Erisa Hirokawa, Fuyu Kobirumaki-Shimozawa, Kotaro Oyama, Seine A. Shintani, Takako Terui, Yasuharu Kushida, Seiichi Tsukamoto, Teruyuki Fujii, Shin'ichi Ishiwata, and Norio Fukuda
  • Journal Title: Prog. Biophys. Mol. Biol. Volume: 124 Pages: 31-40
  • DOI: 10.1016/j.pbiomolbio.2016.09.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant