| Project/Area Number |
17K15566
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General physiology
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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) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | TRPM4 / CaMKII / Arryhthmia / protein interaction / Arrhythmogenicity / arrhythmia / 生理学 / 循環器 |
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| Outline of Final Research Achievements |
Recent studies indicate that increased activity of TRPM4 contributes to acquired arrhythmic changes under stressed conditions. TRPM4 channel activity is strongly modified by Ca2+/calmodulin. We therefore investigated it by noting a potential significance of CaMKII-mediated TRPM4 channel overactivation under disrupted Ca2+ homeostasis.
The possible protein-protein interaction between TRPM4 and CaMKII was tested by the Duolink immunoassay. In order to quantitatively evaluate how CaMKII modifies TRPM4 activation, the gating kinetics of TRPM4 channel on both voltage-dependence and Ca2+ sensitivity were reconstructed. In HL-1 cells, the incidence of early afterdepolarizations (EADs) was increased after incubation with AngII which also activated the CaMKII signalling. Both TRPM4 channel blocker and CaMKII inhibitor could suppress this arrhythmic change. Mathematical simulation also indicated that inhibition of CaMKII may exert anti-arrhythmic effects via suppression of TRPM4 activities.
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| Academic Significance and Societal Importance of the Research Achievements |
In this study, an important mechanism underlying CaMKII-mediated TRPM4 regulation and their kinetic relationships under altered Ca2+-handling was displayed. The simulation described here could facilitate our understanding about electrophysiological changes induced in remodelled cardiomyocytes.
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