Hyperpolarization-activated currents in pulmonary vein cardiomyocytes isolated from human.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16045
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Akita University
• Principal Investigator: Takagi Daichi 秋田大学, 医学部附属病院, 講師 (70723394)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 心房細動 / 肺静脈心筋 / 過分極活性化電流

Outline of Final Research Achievements

Electrophysiological evaluation from human pulmonary vein myocardium showed hyperpolarisation-activated currents blocked by caesium, indicating that human pulmonary vein myocardium also has hyperpolarisation-activated cation currents (funny currents).
The expression levels of protein-coding RNA and long non-coding RNA (lncRNA) in six cardiac regions were analysed by RNA-seq using a portion of the collected specimens. The region most altered in the presence or absence of atrial fibrillation was found to be the pulmonary vein myocardium. Ion channel-related gene sets were significantly enriched in the pulmonary vein myocardium of patients with AF. Cancer-related lncRNAs were also up-regulated in PVs with atrial fibrillation.

Free Research Field

電気生理学

Academic Significance and Societal Importance of the Research Achievements

ヒト肺静脈心筋より、電気生理学的評価を行い、過分極活性化電流を認め、ヒト肺静脈心筋においても過分極活性化陽イオン電流（funny current）を有していることが示された。心不全治療で臨床使用されているイバブラジン（過分極活性化陽イオンチャネル阻害薬）が心房細動発症抑制などに関与する可能性が示唆された。
また、RNA-seqにより6つの心臓領域におけるタンパク質コードRNAとロングノンコードRNA(lncRNA)の発現量を解析し、心房細動の有無で最も変化する部位が肺静脈心筋であることがわかった。がん関連lncRNAなど後天的な遺伝子制御が心房細動の進行に寄与する可能性が示唆された。