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

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06878
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Jikei 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
• Keywords: サルコメア / in vivoイメージング / 心筋 / ナノ計測

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).

Free Research Field

細胞生理学

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。