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

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19459
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Kyoto 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
• 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

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.

Free Research Field

実験病理学

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。