Decreased cardiac pacemaking in TRIC-A knockout mice

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07255
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Hirosaki University
• Principal Investigator: Murakami Manabu 弘前大学, 医学研究科, 教授 (80302090)
• Co-Investigator(Kenkyū-buntansha): 竹島 浩 京都大学, 薬学研究科, 教授 (70212024)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: チャネル / マウス / 遺伝子 / 心臓

Outline of Final Research Achievements

We evaluated the importance of TRIC channels on cardiac pacemaking using TRIC-A-null mice. Although systolic blood pressure (SBP) was not significantly different between wild-type (WT), and TRIC-A-null mice, heart rate (HR) was significantly lower in TRIC-A-null mice than other lines. Isoproterenol (0.3 mg/kg) increased the HR in WT mice, whereas a decreased response in HR was observed in TRIC-A-null mice, suggesting decreased sympathetic responses. Electrocardiography revealed unstable R-R intervals in TRIC-A-null mice. Furthermore, TRIC-A-null mice sometimes showed sinus pauses, suggesting a significant role of TRIC-A channels in cardiac pacemaking. In isolated atrium contraction or action potential recording, TRIC-A-null mice showed decreased response to a β-adrenergic sympathetic nerve agonist (isoproterenol), indicating decreased sympathetic responses. Our study indicates the involvement of TRIC-A channels in cardiac rhythm formation and sympathetic responses.

Free Research Field

循環生理

Academic Significance and Societal Importance of the Research Achievements

本研究により、細胞内カウンターイオンチャネルであるTRICが心臓の洞結節における活動電位発生に関与することが示された。したがって、TRICチャネルを修飾する事により、心拍数を変化させることが可能と考えられた。このことは、TRICが新規抗不整脈薬の標的になり得ることを示唆する。