Elucidation of cardiac excitation-contraction coupling by in vivo nano-imaging

2014 Fiscal Year Final Research Report

• Project/Area Number: 23300146
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurophysiology and muscle physiology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: FUKUDA Norio 東京慈恵会医科大学, 医学部, 准教授 (30301534)
• Co-Investigator(Kenkyū-buntansha): TERUI Takako 東京慈恵会医科大学, 医学部, 助教 (10366247) ; KOBIRUMAKI Fuyu (SHIMOZAWA Fuyu) 東京慈恵会医科大学, 医学部, 助教 (40548905) ; KURIHARA Satoshi 東京慈恵会医科大学, 医学部, 教授 (90057026) ; OHTSUKI Iwao 東京慈恵会医科大学, 医学部, 教授 (70009992)
• Co-Investigator(Renkei-kenkyūsha): ISHIWATA Shin'ICHI 早稲田大学, 理工学術院, 教授 (10130866) ; HIGUCHI Hideo 東京大学, 理学系研究科, 教授 (90165093)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 生理学 / 細胞・組織 / 生体分子 / ナノバイオ / 心筋

Outline of Final Research Achievements

1) In cardiac muscle, a change in sarcomere length (SL) by a mere ~100 nm causes a substantial change in contractility. To accurately analyze the motion of individual sarcomeres with nanometer precision, we developed an experimental system for simultaneous nano-scale analysis of single sarcomere dynamics and intracellular Ca changes via the expression of AcGFP in Z-disks in primary-cultured rat neonatal cardiomyocytes. 2) A rapid increase in temperature to >~38°C induced Ca-independent high-frequency (~10 Hz) sarcomeric auto-oscillations(HSOs) in rat neonatal cardiomyocytes. 3) We developed a high-speed high-resolution in vivo cardiac imaging system in mice. This system enabled three-dimensional analyses of sarcomere dynamics during the cardiac cycle, simultaneously with electrocardiogram and left ventricular pressure measurements. 4) We demonstrated that the Frank-Starling mechanism of the heart was dependent on the “on-off” equilibrium of the thin filament state.

Free Research Field

筋生理学