2021 Fiscal Year Final Research Report
Theoretical and experimental study of controlling cardiac cell system dynamics using HL-1 mouse cardiomyocytes and a mathematical model
Project/Area Number |
19K07290
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 48020:Physiology-related
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Research Institution | Kanazawa Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
九田 裕一 金沢医科大学, 医学部, 講師 (50566916)
津元 国親 金沢医科大学, 医学部, 准教授 (70353331)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | HL-1マウス心筋細胞 / 異常自動能 / 早期後脱分極 / 数理モデル / システム制御 / 分岐解析 / コンピュータシミュレーション |
Outline of Final Research Achievements |
Cardiac abnormal excitability causes tachycardiac arrhythmias leading to sudden death in ischemia and long QT syndrome. In this study, we developed a mathematical model and experimental systems for HL-1 mouse cardiomyocytes to investigate dynamical mechanisms and control approach for abnormal activities. By bifurcation analyses of the mathematical model which can reproduce abnormal activities, we demonstrated that developments of abnormal activities are bifurcation phenomena and proposed reasonable methods of preventing abnormal activities from the aspect of bifurcation theory. Furthermore, we developed experimental systems of HL-1 cells in which abnormal activities can be evoked by modifications of ion channels, demonstrating that experimental results are consistent with theoretical predictions. Our study shows that bifurcation analysis of mathematical models can appropriately define mechanisms of cardiac abnormal activities and may enable us to properly control cardiac arrhythmias.
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Free Research Field |
心臓生理学
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Academic Significance and Societal Importance of the Research Achievements |
虚血やQT延長症候群(LQTS)の心筋に生じる異常自動能は頻脈性不整脈を誘発し突然死の原因となる。本研究では、異常自動能誘発が可能なHL-1マウス心筋細胞の数理モデルと電気生理学的実験系を構築し、異常自動能の発現機序と合理的抑制法を検証した。 理論的解析により、異常自動能を分岐現象として理解できることが示され、その合理的制御方法が分岐制御の観点から的確に予測された。また、HL-1心筋細胞の実験系を用いて異常自動能の発生機序と制御法に関する理論的予測を実験的に検証し、異常自動能の発生機序に基づく合理的制御が可能であることを証明した。これらの成果は、心臓突然死の予防法を確立する上で極めて有用である。
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