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Functional impairment of the heart by flash photolysis of caged compounds - towards an integrated understanding of the critical regions for arrhythmogenesis -

Research Project

Project/Area Number 18K19459
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Tanaka Hideo  京都府立医科大学, 医学(系)研究科(研究院), 教授 (60236619)

Co-Investigator(Kenkyū-buntansha) 熊本 康昭  大阪大学, 工学研究科, 助教 (30611727)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Keywords不整脈 / ケージド化合物 / 光刺激 / 心筋細胞 / カルシウム / ギャップ結合 / 興奮伝導 / 撃発活動
Outline of Final Research Achievements

On the hypothesis that flash photolysis of caged calcium (Ca2+) loaded within cardiac tissue could alter spatiotemporal patterns of impulse generation or conduction, experiments were performed using rapid imaging of the fluo8/AM-based Ca2+ dynamics of the cultured cardiomyocytes monolayer obtained from neonatal rat hearts. It was found that the UV-flash light applied to the myocyte monolayer loaded with caged Ca2+ compounds DMNPE-4/AM resulted in slowing of the impulse conduction near the area of flash application. In addition, some samples showed localized reentrant excitation or abnormal automatic activity of the myocyte monolayer after UV-flash application. Thus, the flash photolysis technique for caged Ca2+ loaded in the myocardium would be a promising approach for modification of the cardiac impulse generation and propagation and for understanding of its basis. In addition, this unique experimental approach could also be worth applying in other biological research fields.

Academic Significance and Societal Importance of the Research Achievements

本研究では、カルシウムイオン(Ca2+)のケージド化合物を付加した心筋組織に紫外光照射することにより、局所のCa濃度を自在に変化させて心筋の興奮伝導を制御できるか否かを検討した。心筋単層培養組織に紫外光を照射できる光学系を構築、ケージドCaのDMNPE-4/AMを付加した心筋組織に紫外光照射することにより心筋組織の興奮や伝導様式を変化させることに成功した。これにより、本手法が心臓の興奮伝導の異常である不整脈の制御や不整脈の発生病理の理解に有用となる可能性が示唆された。光による生物試料の機能制御法は心臓組織に留まらず様々な生命機能を解析する上で革新的な手段となるものと期待できる。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (17 results)

All 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Open Access: 6 results,  Peer Reviewed: 5 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Book (4 results)

  • [Journal Article] Fluorescence imaging of the living heart for understanding the basis of arrhythmias2019

    • Author(s)
      Tanaka H
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 154 Issue: 4 Pages: 171-177

    • DOI

      10.1254/fpj.154.171

    • NAID

      130007726230

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2019 Annual Research Report
    • Open Access
  • [Journal Article] Fluorescence-based Discrimination of Breast Cancer Cells by Direct Exposure to 5-aminolevulinic Acid2019

    • Author(s)
      Morita M, Tanaka H, Kumamoto Y, Nakamura A, Harada Y, Ogata T, Sakaguchi K, Taguchi T, Takamatsu T.
    • Journal Title

      Cancer Med

      Volume: 8 Issue: 12 Pages: 5524-33

    • DOI

      10.1002/cam4.2466

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Terbium ion as RNA tag for slide-free pathology with deep-ultraviolet excitation fluorescence2019

    • Author(s)
      Kumamoto Y, Matsumoto T, Tanaka H, Takamatsu T
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 10745-10745

    • DOI

      10.1038/s41598-019-47353-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Label-free Molecular Imaging and Analysis by Raman Spectroscopy2018

    • Author(s)
      Kumamoto Y, Harada Y, Takamatsu T, Tanaka H
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 51 Issue: 3 Pages: 101-110

    • DOI

      10.1267/ahc.18019

    • NAID

      130007411560

    • ISSN
      0044-5991, 1347-5800
    • Year and Date
      2018-06-26
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bioconjugation strategy for cell surface labelling with gold nanostructures designed for highly localized pH measurement.2018

    • Author(s)
      Leonardo Puppulin, Shigekuni Hosogi, Hongxin Sun, Kazuhiko Matsuo, Toshio Inui, Yasuaki Kumamoto, Toshinobu Suzaki, Hideo Tanaka and Yoshinori Marunaka
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 5278-5278

    • DOI

      10.1038/s41467-018-07726-5

    • NAID

      120006549200

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Label-free evaluation of myocardial infarct in surgically excised ventricular myocardium by Raman spectroscopy2018

    • Author(s)
      Yamamoto T, Minamikawa T, Harada Y, Yamaoka Y, Tanaka H, Yaku H, Takamatsu T
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 14671-14671

    • DOI

      10.1038/s41598-018-33025-6

    • NAID

      120006875669

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Raman microscopic analysis of biological tissues: toward construction of Raman histopathology2020

    • Author(s)
      Harada Y, Tanaka H
    • Organizer
      第97回日本生理学会シンポジウム (誌上発表)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ヒス束ー脚・プルキンエ線維の構造と虚血による不整脈原性2019

    • Author(s)
      松山高明、田中秀央
    • Organizer
      第41回心筋生検研究会学術集会 シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Raman histopathology for living specimens2019

    • Author(s)
      Harada Y, Komatsuzaki T, Tanaka H.
    • Organizer
      Raman Biomedical Raman imaging 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Non-uniform calcium dynamics of the atrial cells and Purkinje fibers with references to T tubules2018

    • Author(s)
      Hideo Tanaka, Taka-aki Matsuyama
    • Organizer
      The 2nd JCS Council Forum on Basic Cardiovascular Research
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Serious heart failure associated with non-compaction cardiomyopathy in a baby of double outlet of right ventricule with left isomerism2018

    • Author(s)
      Matsuyama T, Yamaguchi M, Hasegawa T, Ho SY, Hosoi H, Tanaka H.
    • Organizer
      Weinstein 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 光学顕微鏡の使い方2018

    • Author(s)
      田中秀央
    • Organizer
      第43回組織化学講習会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] カルシウムパラドックスによる心筋拘縮 ラット灌流心における心筋カルシウム動態と細胞構造の解析2018

    • Author(s)
      万井広基、田中秀央
    • Organizer
      生理学研究所研究会2018 「心臓・血管系の頑健性と精緻な制御を支える分子基盤の統合的解明」
    • Related Report
      2018 Research-status Report
  • [Book] 組織細胞化学20192019

    • Author(s)
      中村明宏、田中秀央
    • Total Pages
      12
    • Publisher
      学際企画
    • ISBN
      9784906514946
    • Related Report
      2019 Annual Research Report
  • [Book] 実験医学増刊 「心不全のサイエンス」2019

    • Author(s)
      田中秀央
    • Total Pages
      7
    • Publisher
      羊土社
    • ISBN
      9784758103770
    • Related Report
      2019 Annual Research Report
  • [Book] 実験医学増刊「心不全のサイエンス」2019

    • Author(s)
      田中秀央
    • Total Pages
      220
    • Publisher
      羊土社
    • ISBN
      9784758103770
    • Related Report
      2018 Research-status Report
  • [Book] 組織細胞化学20182018

    • Author(s)
      原田義規、田中秀央
    • Total Pages
      232
    • Publisher
      日本組織細胞化学会
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2023-01-30  

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