Functional analysis of auxiliary subunits of KCNQ1 channels in the heart

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08552
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Jichi Medical University (2018-2020); Osaka Medical College (2017)
• Principal Investigator: NAKAJO Koichi 自治医科大学, 医学部, 教授 (80390699)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: イオンチャネル / KCNQ1チャネル / 複合体 / ゼブラフィッシュ / 修飾サブユニット / KCNEタンパク質 / 電気生理学 / イメージング

Outline of Final Research Achievements

To investigate the in vivo functions of KCNQ1 channels, we identified and isolated the KCNQ1 channel ortholog and its auxiliary subunit KCNE orthologs from the zebrafish cDNA library. It turned out that the KCNE3-like gene from zebrafish was a newly-identified KCNE gene. Furthermore, we confirmed that the new KCNE gene works as a KCNQ1 modulator using Xenopus oocytes as an expression system. We are now analyzing the expression and functions of the new KCNE gene in zebrafish. We are also making transgenic zebrafish that express GFP-tagged KCNQ1 and KCNE genes. It is still a work in progress.
Another result we obtained in the project is that we found the mechanism of how KCNE3 modulates KCNQ1 channels. It has been known that KCNE3 makes the KCNQ1 channel constitutively open channel. By taking advantage of the newly-revealed KCNQ1-KCNE3 structure, we identified several critical amino acid residues in the KCNE3 and S1 segment of the KCNQ1 channel.

Free Research Field

分子生理学

Academic Significance and Societal Importance of the Research Achievements

KCNQ1は心臓、内耳、腎臓、膵臓、胃腸、気管支の上皮細胞など、体中のあらゆる場所に発現する、生理学的に非常に重要なイオンチャネルである。実際、不整脈、難聴、糖尿病などの疾患との関連が知られている。KCNQ1は体の各部位で異なるKCNEサブユニットと複合体を作っていることがしられており、その発現部位、複合体構成を知ることは、KCNQ1チャネルをターゲットとした創薬研究などにおいて重要な意味を持つ。