| Project/Area Number |
23592256
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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 | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Takeshi 山口大学, 大学院医学系研究科, 准教授 (50363122)
YANO Masafumi 山口大学, 大学院医学系研究科, 教授 (90294628)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 悪性高熱症 / 心室頻拍症 / 心不全 / ダントロレン / リアノジン受容体 / カテコラミン誘発性心室頻拍 |
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| Research Abstract |
We previously reported that dantrolene, a therapeutic agent for malignant hyperthermia (MH), prevented abnormal Ca2+ leak by correction of the defective inter-domain interaction between N-terminal and central domains in MH-type RyR. In tachycardia-induced heart failure canine model and catecholaminergic polymorphic ventricular tachycardia (CPVT)-associated RyR2R2474S /+ knock-in (KI) mice model, dantrolene binds to the specific domain in RyR2, and then corrects defective inter-domain interactions within RyR2, subsequently inhibits diastolic Ca2+ leak. In turn, dantrolene improves cardiomyocyte function in failing hearts and prevents bidirectional VT induced by injection of epinephrine or exercise in CPVT. Thus, dantrolene may have a potential to treat heart failure and lethal arrhythmia, specifically targeting RyR2.
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