The analyses of the interaction between the intracellular domains to control the slow deactivation of hERG channel
| Project/Area Number |
17K15567
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General physiology
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| Research Institution | Oita University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| 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 |
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| Outline of Final Research Achievements |
The hERG channel belonging to the voltage-gated potassium channel family has electrostatic interaction sites in the C-terminal cytoplasmic domains. When these electrostatic interaction sites of the hERG channel were disrupted by the mutagenesis, the slow deactivation characteristic were accelerated significantly. In this study, we analyzed these properties of electrostatic interactions to reveal its structure-function relationships. We found that these electrostatic interactions were within the intra-subunit, and that forming them in all subunits was necessary for the slow deactivation. Furthermore, we revealed that the disruption of the electrostatic interactions declined the interaction between the N-terminal- and the C-terminal-cytoplasmic domains, which plays the main role for the mechanisms of the deactivation, leading to an acceleration of the deactivation.
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| Academic Significance and Societal Importance of the Research Achievements |
hERGチャネルは心筋の活動電位の調節に関与し、ヒト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。例えば、突然変異等により、その特徴的な遅い脱活性化に異常が生じると、致死性不整脈のリスクを伴う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。したがって、本研究の成果として得られたhERGチャネルの遅い脱活性化に関する構造機能連関の新しい知見は、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。
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Report
(4 results)
Research Products
(11 results)
