Mechanism and suppression of afterdepolarization-induced arrhythmias in HL-1 cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15016
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: KUDA Yuhichi 金沢医科大学, 医学部, 講師 (50566916)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: HL-1マウス心筋細胞 / 早期後脱分極（EAD) / 遅延後脱分極（DAD) / パッチクランプ / Ca2+測光 / 膜電位

Outline of Final Research Achievements

Atrial fibrillation is the most common arrhythmia and is thought to be induced by afterdepolarizations that occur in cardiomyocytes under a variety of pathological conditions. The aim of this study was to establish an experimental system for cardiomyocytes in which afterdepolarizations could be induced and thereby determine the mechanism and suppression strategy for afterdepolarizations.
Using the whole-cell patch clamp method and fluorescence photometry, we have established an experimental system for HL-1 mouse atrial myocytes in which generation and propagation of action potentials and intracellular Ca2+ transients were recorded. Early and delayed afterdepolarizations could be induced by various modulators of ion channels and transporters in this system. This experimental system is useful in analyzing mechanisms for afterdepolarization-induced arrhythmias systematically and is expected to be applied to future studies using human iPS cell-derived cardiomyocytes.

Free Research Field

心臓生理学

Academic Significance and Societal Importance of the Research Achievements

後脱分極発生機序の動物心筋を用いた電気生理学的解析は以前から行われているが、全て実験条件の異なる個別的研究であり、後脱分極発生機序の統合的理解は未だなされていない。近年、iPS細胞由来心筋細胞を用いた研究が盛んになっているが、継代培養できない細胞での体系的研究は困難であり、後脱分極発現機構の本質的理解やその合理的抑制方法の解明には新たな実験系が必要である。本研究により培養HL-1心筋細胞を用いた継続的かつ体系的な電気生理学的研究が可能な実験系が確立され、後脱分極の発生機序と抑制方法の統合的検証が可能となった。本研究の成果は、不整脈の予防・治療法の開発に繋がるものであり、臨床的にも重要である。