| Project/Area Number |
26702014
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Research Collaborator |
MOHRI Satoshi 川崎医科大学, 医学部, 教授 (00294413)
HASHIMOTO Ken 川崎医科大学, 医学部, 講師 (80341080)
HANASHIMA Akira 川崎医科大学, 医学部, 助教 (70572981)
KATANOSAKA Yuki 岡山大学, 大学院医歯(薬)学総合研究科, 助教 (60432639)
HONDA Takeshi 川崎医科大学, 医学部, 大学院生
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥23,270,000 (Direct Cost: ¥17,900,000、Indirect Cost: ¥5,370,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2014: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
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| Keywords | バイオメカニクス / メカノバイオロジー / メカノフィジオロジー / リモデリング / カルシウム / ホメオスタシス / T管膜 / 心不全 / Na+/Ca2+交換体 / T管 / 心筋細胞 / 細胞バイオメカニクス / Ca2+ / メカニカルストレス / NCX1 / 心筋リモデリング |
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| Outline of Final Research Achievements |
Transverse tubules (T-tubules) are invaginations of the sarcolemma and critical for cardiomyocyte contraction. Therefore, T-tubule disorganization is linked to decreased contractility in heart failure. However, the molecular details have remained unclear. Na+/Ca2+ exchanger (NCX1) is essential Ca2+ regulator of myocyte Ca2+ homeostasis and preferentially localized to T-tubule membrane. We found that NCX1 activity was depressed before T-tubule disorganization during the progression of heart failure induced by pressure overload. In addition, the recovery of depressed NCX1 activity by inducing NCX1 expression prevented T-tubule disorganization and heart failure progression. These results suggest that local Ca2+ control beneath the T-tubule membrane is crucial for the maintenance of myocyte structure and function, in which NCX1 has a pivotal role.
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