心筋KCNQ1チャネル分子複合体の病態生理学的役割に関する研究

• Published in: 日本薬理学会年会要旨集 p. 2-B-P-135
• Main Authors: 野間口, 財, 岩鶴, 果奈, 永森, 收志, 黒川, 洵子, 児玉, 昌美, 服部, 希海, 杉本, 早穂, 坂本, 多穗, 渡邉, 泰秀, 清水, 聡史
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: cardiac myocyte; heart; ion channel
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_2-B-P-135

The IKs channels, which contribute to the repolarization phase of the cardiac action potential, are composed of the alpha subunit KCNQ1 and beta subunit KCNE1. Mutations in these genes are associated with the development of lethal arrhythmias due to congenital QT prolongation syndrome and are influenced by sympathetic nerve stimulation and sex hormones. As a molecular mechanism, we have demonstrated the involvement of a molecular complex of the KCNQ1 channel in the IKs regulation by intracellular Ca2+, cAMP, and NO. Recently, membrane proteomics has shown an association between the KCNQ1 molecular complex and Ca2+ signaling, but the pathophysiological role of this association has not been elucidated. Therefore, we aimed to test whether IKs channels activated by pathological Ca2+ overload may compensate for arrhythmias using genetically engineered (IKs-Tg) mice expressing cardiac human IKs channels. We employed a sepsis model for pathological Ca2+ overload condition. We found that the sepsis score IKs-Tg mice was significantly lower than that in wild-type mice, suggesting a protective role of the IKs channel on cardiac pathological modification by sepsis.