High-speed three dimensional spatial imaging analysis of cell and tissue interactions involved in the generation and propagation of automatic activity in the pulmonary vein myocardium

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Toho University
• Principal Investigator: NAMEKATA Iyuki 東邦大学, 薬学部, 准教授 (30510309)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 薬理学 / イメージング / 肺静脈心筋 / 心房細動 / 自動能 / 抗不整脈薬

Outline of Final Research Achievements

We recorded the spontaneous automaticity from the myocardial layer of isolated pulmonary veins with high-speed 3-dimensional confocal microscopy and glass microelectrode technique. In this study, the role of the Na current in the automaticity of the pulmonary vein myocardium was examined in isolated guinea pig pulmonary vein cardiomyocytes and tissue preparations. GS-458967 inhibited the persistent component of the Na current (late INa) and suppressed the automaticity of the pulmonary vein myocardium. Pilsicainide inhibited only the transient component of Na current (peak INa) and had no effect on the firing frequency. Similarly, class I antiarrhythmic drugs which block the late INa inhibited the automaticity. NCC-3902, selective blockers of late INa, inhibited the automatic activity of the pulmonary vein myocardium, which appears to be promising as a drug for the pharmacological treatment of atrial fibrillation.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

心房細動は心房が1分間に400-600回程度の高頻度で不規則に細かく震える不整脈であり、我が国には約130万人の患者が存在するといわれている。本研究は心房細動の発生源として重要視されている肺静脈の電気的自発活動に焦点を当て、組織の立体構造を保持した肺静脈標本に高速３次元共焦点顕微鏡法を適用し、細胞から組織レベルまでの総合的視点から、自発活動の発生および伝播機序を解明することを目的とする。本研究で得られる成果は、心臓における自動能の理解を深めるとともに、心房細動発生機序の解明および新しい治療薬開発への展開が期待でき、学術的・社会的に意義のある研究である。