Elucidation of cardiac regulatory mechanisms by in vivo nano-imaging

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04677
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General 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): 照井 貴子 東京慈恵会医科大学, 医学部, 助手 (10366247) ; 小比類巻 生 東京慈恵会医科大学, 医学部, 助教 (40548905) ; 大山 廣太郎 東京慈恵会医科大学, 医学部, 特別研究員 (70632131)
• Co-Investigator(Renkei-kenkyūsha): ISHIWATA SHIN'ICHI 早稲田大学, 理工学術院, 名誉教授 (10130866)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 生物物理 / ナノバイオ / 分子イメージング / 心筋 / 細胞・組織

Outline of Final Research Achievements

1) We performed simultaneous nano-imaging of intracellular Ca dynamics and single sarcomere length in rat neonatal cardiomyocytes, via expression of α-actinin-YC-Nano140 in the Z disks. 2) We developed a high-precision method for the evaluation of the intracellular Ca dynamics in the isolated perfused mouse heart. 3) We developed a high speed (100 fps), high resolution (20 nm) nano-imaging system for myocardial sarcomeres in living mice. Using this system, we conducted three-dimensional analysis of sarcomere dynamics in left ventricular myocytes during the cardiac cycle, simultaneously with electrocardiogram and left ventricular pressure measurements. 4) We analyzed the mechanical properties of single sarcomere dynamics during sarcomeric auto-oscillations (Ca-SPOC) in myofibrils from donor hearts and from patients with severe dilated cardiomyopathy (DCM). Sarcomere dynamics was found to be depressed in DCM myofibrils, due to impairment of thick-thin filament sliding.

Free Research Field

生理学