| Project/Area Number |
20K16126
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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 48020:Physiology-related
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| Research Institution | Fukuoka University |
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Principal Investigator |
Hu Yaopeng 福岡大学, 医学部, 助教 (40708476)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | TRPM4 / Nav1.5 / Arrhythmogenicity / Conduction disturbance / Conduction disturbances / Purkinje fibers / Numerical simulation / Conduction block / Arrhythmia / Nav1.5 channel / TRPM4 channel |
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| Outline of Research at the Start |
The present study will address the implications of the Nav1.5-TRPM4 interaction by biochemical and electrophysiological experiments, offering an new knowledge about the molecular mechanism for arrhythmias which show a complex multi-genetic background and overlapping phenotypes such as LQTS and BrS.
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| Outline of Final Research Achievements |
Compelling evidence suggests that the critical cardiac Nav1.5 channel interacts with various proteins, which regulate its expression and functionality. This study has shown a protein complex formation between Nav1.5 and TRPM4 within the myocardium. Additionally, we explored mutations in the TRPM4 channel, identified through genomic analysis of familial atrioventricular conduction block, using both experimental and numerical simulation approaches. By integrating the results from gating analysis into a Purkinje fiber cardiomyocyte model for simulations, we noted that the augmented activity of TRPM4 mutant channels, along with tissue heterogeneity, significantly modified Nav1.5 function, causing complex abnormalities in excitation propagation. These results offer valuable insights into how TRPM4 anomalies or malfunctions might affect Nav1.5 activity in cardiomyocytes, potentially leading to disturbances in normal cardiac excitation and conduction patterns.
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| Academic Significance and Societal Importance of the Research Achievements |
これらの研究結果は、心筋細胞においてTRPM4とNav1.5がタンパク質複合体として存在することを示しており、膜タンパク質TRPM4チャネルの輸送障害や機能不全がNav1.5の機能にどのような影響を及ぼすか、つまり正常な心臓の興奮や伝導に乱れが生じる可能性について、興味深い示唆を与えている。
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