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

Research Project

Project/Area Number 23300146
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurophysiology and muscle physiology
Research InstitutionJikei 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)
大山 廣太郎  早稲田大学, 理工学術院, 助教 (70632131)
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
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
Fiscal Year 2014: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2012: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2011: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords生理学 / 細胞・組織 / 生体分子 / ナノバイオ / 心筋 / 筋肉生理学 / 分子・細胞生理学 / 分子心臓学 / 生物物理学 / バイオイメージング / ナノバイオシステム / 1分子イメージング・ナノ計測 / 医用物理学 / 生物物理一般 / 生物物理
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.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (49 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (36 results) (of which Invited: 10 results) Book (1 results)

  • [Journal Article] High-frequency sarcomeric auto-oscillations induced by heating in living neonatal cardiomyocytes of the rat2015

    • Author(s)
      Shintani, S., Oyama, K. Fukuda, N., and Ishiwata, S.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 457 Issue: 2 Pages: 165-170

    • DOI

      10.1016/j.bbrc.2014.12.077

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sarcomere length nanometry in rat neonatal cardiomyocytes expressed with α-actinin-AcGFP in Z-discs2014

    • Author(s)
      Shintani, S., Oyama, K., Kobirumaki, F., Shimozawa, F., Ohki, T., Ishiwata, S., and Fukuda, N.
    • Journal Title

      J. Gen. Physiol.

      Volume: 143 Issue: 4 Pages: 513-524

    • DOI

      10.1085/jgp.201311118

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac thin filament regulation and the Frank-Starling mechanism2014

    • Author(s)
      Fuyu Kobirumaki-Shimozawa, Inoue, T. Shintani, S., Oyama, K., Terui, T. Minamisawa, S., Ishiwata, S., and Fukuda, N.
    • Journal Title

      J. Physiol. Sci.

      Volume: 64 Issue: 4 Pages: 221-232

    • DOI

      10.1007/s12576-014-0314-y

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical definition and diagnostic criteria for sarcopenia2014

    • Author(s)
      Udaka J, Fukuda N, Yamauchi H, Marumo K.
    • Journal Title

      The Journal of Physical Fitness and Sports Medicine

      Volume: 3 Issue: 3 Pages: 347-352

    • DOI

      10.7600/jpfsm.3.347

    • NAID

      130004972984

    • ISSN
      2186-8123, 2186-8131
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Depressed Frank-Starling mechanism in the left ventricular muscle of the knock-in mouse model of dilated cardiomyopathy with troponin T deletion mutation ΔK2102013

    • Author(s)
      Inoue T, Kobirumaki-Shimozawa F, Kagemoto T, Fujii T, Terui T, Kusakari Y, Hongo K, Morimoto S, Ohtsuki I, Hashimoto K, Fukuda N
    • Journal Title

      J Mol Cell Cardiol.

      Volume: 63 Pages: 69-78

    • DOI

      10.1016/j.yjmcc.2013.07.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Qualitative changes in sarcomeric ultrastructure in skeletal muscle atrophy2013

    • Author(s)
      Udaka J, Fukuda N, Kurihara S, Marumo K
    • Journal Title

      Bone Joint Nerve

      Volume: 3 Pages: 33-38

    • NAID

      40020260964

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 筋萎縮に伴うサルコメアの質的変化2013

    • Author(s)
      宇高 潤,、福田 紀男、栗原 敏、丸毛 啓史
    • Journal Title

      Bone Joint Nerve

      Volume: 3 Pages: 33-38

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sarcomere imaging by quantum dots for the study of cardiac muscle physiology.2012

    • Author(s)
      Kobirumaki-Shimozawa, F., Ishiwata, S., et al.
    • Journal Title

      J. Biomed. Biotech.

      Volume: 2012 Pages: 313814-313814

    • DOI

      10.1155/2012/313814

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microscopic heat pulses induce contraction of cardiomyocytes without calcium transients2012

    • Author(s)
      Kotaro Oyama
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 417 Issue: 1 Pages: 607-612

    • DOI

      10.1016/j.bbrc.2011.12.015

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thin filament-reconstituted skinned muscle fibers for the study of muscle physiology.2011

    • Author(s)
      Higuchi S
    • Journal Title

      J Biomed Biotechnol.

      Volume: 2011 Issue: 1 Pages: 486021-486021

    • DOI

      10.1155/2011/486021

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sarcomere length-dependent Ca(2+) activation in skinned rabbit psoas muscle fibers : coordinated regulation of thin filament cooperative activation and passive force2011

    • Author(s)
      Fukuda, N., Ishiwata, S., et al
    • Journal Title

      JOURNAL OF PHYSIOLOGICAL SCIENCES

      Volume: 61(6) Issue: 6 Pages: 515-523

    • DOI

      10.1007/s12576-011-0173-8

    • NAID

      10030351129

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Real-time measurement of the length of a single sarcomere in rat ventricular myocytes : a novel analysis with quantum dots2011

    • Author(s)
      Fukuda N, Inoue T, Yamane M, Terui T, Kobirumaki F, Ohtsuki I, Ishiwata S, Kurihara S
    • Journal Title

      American Journal of Physiology Cell Physiology

      Volume: 301

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] High-frequency sarcomeric auto-oscillations in living cardiomyocytes under hyperthermal conditions2014

    • Author(s)
      Shintani, S.A., Oyama, K., Fukuda, N., Ishiwata, S.
    • Organizer
      第52回日本生物物理学会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ナノスケール高速ライブイメージングによるin vivoサルコメア計測2014

    • Author(s)
      小比類巻生、大山廣太郎、下澤東吾、照井貴子、南沢享、石渡信一、福田紀男
    • Organizer
      第12回ナノ学会大会
    • Place of Presentation
      京都大学宇治キャンパス
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] サルコメア長ナノ計測による心筋細胞内収縮ダイナミクスの系統的解明2014

    • Author(s)
      新谷正嶺、大山廣太郎、石渡信一、福田紀男
    • Organizer
      第12回ナノ学会大会
    • Place of Presentation
      京都大学宇治キャンパス
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 高精度分子イメージングを用いた心臓拍動メカニズムの解析2014

    • Author(s)
      福田紀男
    • Organizer
      革新的分子イメージングで拓く医学新領域
    • Place of Presentation
      東京工業大学
    • Year and Date
      2014-04-22
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Real-time imaging of single sarcomeres in the mouse heart in vivo2014

    • Author(s)
      Norio Fukuda
    • Organizer
      International Symposium on Nanomedicine Molecular Science
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] THERMAL ACTIVATION OF CARDIAC THIN FILAMENTS INDUCES CONTRACTION WITHOUT INTRACELLULAR CA2+ CHANGES: STUDIES WITH CARDIOMYOCYTES AND AN IN VITROMOTILITY ASSAY2014

    • Author(s)
      Kotaro Oyama, Shuya Ishii, Tomomi Arai, Seine A. Shintani, Hideki Itoh, Norio Fukuda, Madoka Suzuki, Shin’ichi Ishiwata
    • Organizer
      米国生物物理学会
    • Place of Presentation
      San Francisco, Moscone Center
    • Related Report
      2013 Annual Research Report
  • [Presentation] SIMULTANEOUS IMAGING OF LOCAL CALCIUM AND SINGLE SARCOMERE LENGTH IN RAT NEONATAL CARDIOMYOCYTES VIA EXPRESSION OF CAMELEON-NANO IN Z-DISCS.2014

    • Author(s)
      Seiichi Tsukamoto, Kotaro Oyama, Seine A. Shintani, Norio Fukuda, Shin’ichi Ishiwata
    • Organizer
      米国生物物理学会
    • Place of Presentation
      San Francisco, Moscone Center
    • Related Report
      2013 Annual Research Report
  • [Presentation] REAL-TIME INTRACELLULAR CALCIUM IMAGING IN THE HEART2014

    • Author(s)
      Erisa Hirokawa, Kotaro Oyama, Takako Terui, Togo Shimozawa, Shin’ichi Ishiwata, Norio Fukuda
    • Organizer
      米国生物物理学会
    • Place of Presentation
      San Francisco, Moscone Center
    • Related Report
      2013 Annual Research Report
  • [Presentation] SARCOMERE LENGTH NANOMETRY IN CARDIOMYOCYTES EXPRESSEDWITHα-ACTININ-ACGFP IN Z-DISCS2014

    • Author(s)
      Seine A. Shintani, Kotaro Oyama, Takashi Ohki, Shin’ichi Ishiwata, Norio Fukuda
    • Organizer
      米国生物物理学会
    • Place of Presentation
      San Francisco, Moscone Center
    • Related Report
      2013 Annual Research Report
  • [Presentation] REAL-TIME IMAGING OF SARCOMERE DYNAMICS IN THE MOUSE HEART IN VIVO.2014

    • Author(s)
      Fuyu Kobirumaki-Shimozawa, Kotaro Oyama, Akari Mizuno, Takako Terui, Togo Shimozawa, Takashi Ohki, Shin’ichi Ishiwata, Norio Fukuda
    • Organizer
      米国生物物理学会
    • Place of Presentation
      San Francisco, Moscone Center
    • Related Report
      2013 Annual Research Report
  • [Presentation] 局所熱パルス法を用いて細胞の温度感受性を解明する2014

    • Author(s)
      大山廣太郎 、新谷正嶺、伊藤秀城、石井秀弥、福田紀男、鈴木 団、石渡信一
    • Organizer
      日本生理学会
    • Place of Presentation
      鹿児島大学
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 高速ライブイメージングを用いたマウス in vivo 単一サルコメア計測2014

    • Author(s)
      小比類巻 生、大山廣太郎、広川恵里沙、下澤東吾、照井貴子、南沢 享、石渡信一、福田紀男
    • Organizer
      日本生理学会
    • Place of Presentation
      鹿児島大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] Yellow Cameleon-Nano を用いたラット幼若心筋細胞のサルコメア長とカルシウムの同時観測2014

    • Author(s)
      塚本精一、大山廣太郎、新谷正嶺、小比類巻 生、石渡信一、福田紀男
    • Organizer
      日本生理学会
    • Place of Presentation
      鹿児島大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] α-actinin-AcGFP を Z 線に発現させた心筋細胞におけるサルコメア長のナノ精度計測系2014

    • Author(s)
      新谷正嶺、大山廣太郎、大木高志、石渡信一、福田紀男
    • Organizer
      日本生理学会
    • Place of Presentation
      鹿児島大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] ストレスファイバー様構造を形成したラット幼若心筋細胞のサルコメア動態の解析2014

    • Author(s)
      藤井輝之、新谷正嶺、塚本精一、石渡信一、福田紀男 、南沢 享
    • Organizer
      日本生理学会
    • Place of Presentation
      鹿児島大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 生きたマウスの心臓における単一サルコメア長解析2013

    • Author(s)
      小比類巻生、大山廣太郎、照井貴子、水野紅理、影本達也、下澤東吾、 石渡信一、福田紀男
    • Organizer
      ナノ学会
    • Place of Presentation
      東京工業大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] nm 精度のサルコメア収縮動態イメージングによる新規実験系の構築2013

    • Author(s)
      新谷正嶺、大山廣太郎、大木高志、石渡信一、福田紀男
    • Organizer
      ナノ学会
    • Place of Presentation
      東京工業大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 高精度分子イメージングによる心筋収縮機序解明2013

    • Author(s)
      福田紀男
    • Organizer
      高精度分子イメージングで拓く医学新領域
    • Place of Presentation
      東京医科歯科大学
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] High-resolution analysis of sarcomeric auto-oscillations in rat neonatal cardiomyocytes2013

    • Author(s)
      Seine A. Shintani, Kotaro Oyama, Shin’ichi Ishiwata, Norio Fukuda
    • Organizer
      日本生物物理学会
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2013 Annual Research Report
  • [Presentation] Simultaneous imaging of intracellular Ca2+ and sarcomere length in neonatal cardiomyocytes via expression of cameleon-Nano in Z-discs2013

    • Author(s)
      Seiichi Tsukamoto, Kotaro Oyama, Seine Shintani, Fuyu Kobirumaki , Shin’ichi Ishiwata, Norio Fukuda
    • Organizer
      日本生物物理学会
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2013 Annual Research Report
  • [Presentation] Real-time high-resolution cardiac imaging in vivo2013

    • Author(s)
      Fuyu Kobirumaki-Shimozawa, Kotaro Oyama, Seine A. Shintani, Erisa Hirokawa, Togo Shimozawa, Takako Terui, Shin'ichi Ishiwata, Norio Fukuda
    • Organizer
      日本生物物理学会
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Real-time imaging of single sarcomeres in the mouse heart in vivo2013

    • Author(s)
      福田紀男
    • Organizer
      ナノメディシン分子科学国際シンポジウム
    • Place of Presentation
      東京大学
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] In vivoナノイメージングによる心筋収縮機構の解析2013

    • Author(s)
      福田紀男
    • Organizer
      日本バイオマテリアル学会
    • Place of Presentation
      東京都、タワーホール船堀
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Nano-imaging of sarcomeres in the heart in vivo -Basis for Cardiac Nanophysiology and Nanomedicine-2013

    • Author(s)
      福田紀男
    • Organizer
      台湾-日本ナノメディシン研究会
    • Place of Presentation
      台北
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 心筋サルコメアイメージングの試み2012

    • Author(s)
      照井貴子、小比類巻生、水野紅里、影本達也、下澤東吾、石渡信一、栗原敏、福田紀男
    • Organizer
      日本生理学会
    • Place of Presentation
      長野県松本市
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 幼若ラット心筋細胞におけるサルコメア自励振動(SPOC)特性と電気刺激応答拍動の関係性2012

    • Author(s)
      新谷正嶺、山根光智、大山廣太郎、栗原敏、石渡信一、福田紀男
    • Organizer
      日本生理学会
    • Place of Presentation
      長野県松本市
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 局所熱パルスはカルシウム濃度上昇を伴わずに心筋細胞の収縮を誘発する2012

    • Author(s)
      大山廣太郎、水野紅里、新谷正嶺、伊藤秀城、芹澤隆博、福田紀男、鈴木団、石渡信一
    • Organizer
      日本生理学会
    • Place of Presentation
      長野県松本市
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] スキンド標本を用いた拡張型心筋症マウスにおける筋長効果減弱のメカニズム2012

    • Author(s)
      井上天宏、草刈洋一郎、本郷賢一、森本幸生、大槻磐男、栗原敏、福田紀男
    • Organizer
      日本生理学会
    • Place of Presentation
      長野県松本市
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 心筋会2012

    • Author(s)
      福田紀男
    • Organizer
      心筋の収縮機構に関する最近の知見について -ナノとマクロの融合-
    • Place of Presentation
      慶應義塾大学(東京)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Real-time measurement of sarcomere length in the mouse heart in vivo by using α-actinin-GFP2012

    • Author(s)
      Akari Mizuno, Fuyu Kobirumaki-Shimozawa, Kotaro Oyama, Takako Terui, Erisa Hirokawa, Togo Simozawa, Shin’ichi Ishiwata, Norio Fukuda
    • Organizer
      日本生物物理学会
    • Place of Presentation
      名古屋大学
    • Related Report
      2012 Annual Research Report
  • [Presentation] The effects of disease and aging on human myocardial SPOC2012

    • Author(s)
      Tatsuya Kagemoto, Mitsunori Yamane, Cristobal G. Dos Remedios, Norio Fukuda, Shin’ichi Ishiwata
    • Organizer
      日本生物物理学会
    • Place of Presentation
      名古屋大学
    • Related Report
      2012 Annual Research Report
  • [Presentation] Ca2+-independent on-off regulation of a cardiomyocyte by microscopic heat pulses2012

    • Author(s)
      Kotaro Oyama, Akari Mizuno, Seine Shintani, Hideki Itoh, Takahiro Serizawa, Norio Fukuda, Madoka Suzuki, Shin’ichi Ishiwata
    • Organizer
      日本生物物理学会
    • Place of Presentation
      名古屋大学
    • Related Report
      2012 Annual Research Report
  • [Presentation] Auto-oscillation (SPOC) properties of sarcomeres in rat neonetal cardiomyocytes2012

    • Author(s)
      Seine Shintani, Kotaro Oyama, Norio Fukuda , Shin'ichi Ishiwata
    • Organizer
      日本生物物理学会
    • Place of Presentation
      名古屋大学
    • Related Report
      2012 Annual Research Report
  • [Presentation] 量子ドットを利用した心筋の拍動解析2011

    • Author(s)
      福田紀男、芹澤隆博、照井貴子、下澤東吾、小比類巻生、影本達也、石渡信一、栗原敏
    • Organizer
      ナノ学会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2011-06-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] α-Actinin-GFPを用いたアダルト心筋細胞のサルコメア長計測2011

    • Author(s)
      小比類巻生、照井貴子、水野紅理、影本達也、下澤東吾、石渡信一、栗原敏、福田紀男
    • Organizer
      ナノ学会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2011-06-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] 高精度分子イメージングを用いたin vivo心収縮メカニズムの解析

    • Author(s)
      福田紀男
    • Organizer
      第21回JSPPPEC ミーティング
    • Place of Presentation
      東京慈恵会医科大学
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] メカノバイオロジー(第12章:横紋筋のメカノバイオフィジックス:マクロからミクロへ)2015

    • Author(s)
      石渡信一、島本勇太、福田紀男
    • Total Pages
      13
    • Publisher
      化学同人
    • Related Report
      2014 Annual Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

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