2017 Fiscal Year Final Research Report
Novel therapy of arrhythmia targeting key domain in ryanodine receptor
| Project/Area Number |
15K09085
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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 |
Cardiovascular medicine
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小田 哲郎 山口大学, 医学部附属病院, 助教 (40569290)
小林 茂樹 山口大学, 大学院医学系研究科, 准教授 (90397993)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | リアノジン受容体 / カルモジュリン |
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| Outline of Final Research Achievements |
Applicants made 28 kinds of peptides incorporating point mutations in the peptide of CaM BD. Among the mutated peptides of many prepared CaM BDs, those with the strongest binding to CaM were screened by two methods. The creation of KI mouse incorporating the CaM high affinity RyR2 mutation incorporating the selected mutation was completed and the affinity of RyR2 and CaM was high in this mouse and it was found that CaM was not easily removed from RyR2 even when phosphorylated. Arrhythmia in CaM high affinity KI mice: Multiplying CaI high-affinity RyR2 mutated KI mice with RyR-R 2474 S CPVT mice resulted in a dramatic decrease in exercise burden and arrhythmia frequency at drug loading.
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| Free Research Field |
循環器内科学
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