2020 Fiscal Year Final Research Report
Electrophysiological analysis of pathogenesis and effective therapy for early repolarization syndrome
| Project/Area Number |
19K17593
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Takayama Koichiro 国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (20816988)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | 早期再分極症候群 / KCND3変異 / 一過性外向きカリウム電流 / 機能獲得型障害 / キニジン / ベプリジル / 疾患モデルiPS細胞 |
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| Outline of Final Research Achievements |
Early repolarization syndrome (ERS) is one of the diseases which cause sudden cardiac death in young people. I detected a new KCND3 heterozygous mutation, p.Gly306Ala, in one of 11 ERS patients. In electrophysiological analysis using cultured cells expressing mutant Kv4.3 encoded by KCND3, I found that the mutation caused gain-of-function disorder of transient outward potassium current (Ito) produced by Kv4.3, and that quinidine and bepridil, which were Ito blockers, concentration-dependently restored the disorder. For the further experiment, I established a human iPS cell model of ERS with the KCND3 mutation by genome editing and succeeded in setting up an experimental system using cardiomyocytes differentiated from the iPS cells.
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| Free Research Field |
循環器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
ERSは比較的新しい疾患概念のため未解明な部分が多い。本研究成果は、原因遺伝子の同定、電気生理学的な病態解明、薬の効果発現のメカニズム解明において貢献できた。今後は、KCND3遺伝子検査によって、原因不明の特発性心室細動患者の正確な診断が可能となり、キニジンなどの適切な薬剤を使用することで若年者心臓突然死を予防することができるだろう。
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