Roles of molecular complex of IKs channel in plasma membrane depolarization - relaxation coupling in cardiac myocytes

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06683
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kodama Masami 東京大学, 定量生命科学研究所, 特任研究員 (30512248)
• Co-Investigator(Kenkyū-buntansha): 黒川 洵子 静岡県立大学, 薬学部, 教授 (40396982)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: イオンチャネル / 心筋細胞

Outline of Final Research Achievements

The slow component of delayed rectifier potassium (IKs) channel regulates repolarization process. We employed a transgenic mouse overexpressing human IKs channel to identify IKs channel interacting proteins comprehensively with immunological technique and proteomic analysis. We identified 163 proteins as potential IKs channel binding partners, including whose biofunction were “Calcium signaling”, such as Na+-Ca2+ exchange transporter (NCX1). GST pull down assay showed that a C-terminus of IKs channel contributed the interaction with NCX1 regardless of [Ca2+]. The interaction between IKs channel and NCX1 was also detected in human iPS cell-derived cardiomyocytes and cardiomyocytes of wild type guinea pig or dog, suggesting that molecular complex of IKs channel with NCX1 was widely common among mammal cardiomyocytes.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

心筋興奮終焉期も再分極過程と筋弛緩は同期しているにも関わらず、興奮初期の興奮収縮連関のように、活動電位と細胞内Ca2+濃度が連関するかについての報告はない。本研究でIKsチャネルとの相互作用を見出したNCX1は、コードする遺伝子が、ゲノムワイド関連解析で、再分極相の延長による不整脈発作を所見とするQT延長症候群に感受性があることが報告されており注目に値する。両者の相互作用はヒトでも見いだされており、機能連関の解析を経て、心筋の恒常的な電気活動とその破綻である不整脈におけるIKsチャネル分子複合体の生理的意義を明らかにしたい。