The elucidation of mechanisms underlying triggered activity in inheritable lethal arrhythmias: in silico predictions
| Project/Area Number |
16KT0194
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 特設分野 |
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| Research Field |
Complex Systems Disease Theory
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| Research Institution | Kanazawa Medical University (2018)
Osaka University (2016-2017) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
倉智 嘉久 大阪大学, 医学系研究科, 教授 (30142011)
芦原 貴司 滋賀医科大学, 医学部, 講師 (80396259)
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| Project Period (FY) |
2016-07-19 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 生理学 / 循環器・高血圧 / 細胞・組織 / 生物物理 / 興奮伝播 / 心筋細胞 / 活動電位 / ソフトコンピューティング |
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| Outline of Final Research Achievements |
It is believed that arrhythmias in patients with long QT syndrome, heart failure, and Brugada syndrome are caused by a triggered activity that preceded the arrhythmia onset. For instance, cardiac action potential with transient depolarizations that occurs during action potential (AP) phase 2 to 3 (early afterdepolarization) is a typical example of the triggered activity. Furthermore, an AP shortening followed by re-excitation, which is referred to as phase-2 reentry, is the triggering mechanism of ventricular fibrillation in the Brugada syndrome. We showed that a combination of selective reduction of cardiac sodium channel expression from the lateral membrane in each cardiomyocyte and spatial dispersion of sodium channel expression in the ventricle is responsible for phase-2 reentry mechanism. Furthermore, we elucidated that reactivation of L-type calcium channel current accompanying excessive prolongation of AP leads to the development of early afterdepolarization.
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| Academic Significance and Societal Importance of the Research Achievements |
心室頻拍や心室細動といった心室性不整脈は、突然死をもたらす。これらの致死性不整脈の発生に先行して、発症のきっかけとなる応答（トリガー）が発生する。このトリガーの発生を予測し、抑止できれば、心臓突然死の危険性を低減できる。本研究では、不整脈トリガーの発生機序を解明し、新たな不整脈発生予測法の開発に資する重要な成果を得た。本成果は、致死性不整脈の誘発制御理論の確立に向けた礎となる。
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Report
(4 results)
Research Products
(40 results)
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[Journal Article] Integrative and theoretical research on the architecture of a biological system and its disorder2019
Author(s)
Shinichi Uchida, Yoshiyuki Asai, Yoshiaki Kariya, Kunichika Tsumoto, Hiroshi Hibino, Masashi Honma, Takeshi Abe, Fumiaki Nin, Yasutaka Kurata, Kazuharu Furutani, Hiroshi Suzuki, Hiroaki Kitano, Ryuji Inoue, Yoshihisa Kurachi
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Journal Title
The Journal of Physiological Sciences
Volume: 69
Issue: 3
Pages: 443-451
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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