Analyses of the structure-function relationship based on the characteristic interaction among the intracellular domains in the hERG channel

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16491
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Oita University
• Principal Investigator: Kume Shinichiro 大分大学, 医学部, 助教 (90794579)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: イオンチャネル / hERGチャネル / 構造機能連関 / 分子生物学 / 電気生理学

Outline of Final Research Achievements

The hERG channel is a member of voltage-gated potassium channel and has a unique assembly "Non-domain swapped structure" which supposedly interacts between the voltage sensor domain (VSD) and a pore domain (PD) in the same domain. In this study, I demonstrated the features of the intracellular domains associated with this characteristic structure; the direct interaction of S4-S5 linker domain located between VSD and PD with C-linker domain in C-terminal region, which suggests that this intracellular interaction plays an important role in slow deactivation.
In addition, I applied the experiment technique of this study and analyzed the effects of drugs on this channel.

Free Research Field

イオンチャネルの分子生理学

Academic Significance and Societal Importance of the Research Achievements

hERGチャネルはヒト心室筋の活動電位における再分極の調節に関与しており、心臓の正常な生理機能において極めて重要な役割を担う。そのため、遺伝子の異常や薬剤の投与により機能不全が生じると、心室性不整脈や突然死のリスクを伴うQT延長症候群のような疾患の原因となり得ることが知られている。本研究により得られたhERGチャネルの構造機能連関に関する成果や薬物投与の影響に関する成果は、イオンチャネル研究の発展に役立つだけでなく、このようなヒト心臓の疾患に対する予防や治療への貢献も期待できる。