| Project/Area Number |
22590204
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
OMATSU Mariko (KANBE Mariko) 滋賀医科大学, 医学部, 准教授 (80161397)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUURA Hiroshi 滋賀医科大学, 医学部, 教授 (60238962)
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| Research Collaborator |
YAMAMOTO Takefumi 滋賀医科大学, 医学部, 技術職員
MORI Yasuhiro 滋賀医科大学, 医学部, 技術職員
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ACMs / novel heart cells / self-beating / atypically-shaped cardiomyocytes / cardiomyocytes / autophagy / ischemia / calcium transients / novel heart cell / cardiomyocyte / cardiac ventricle / Ca2+ transients / automaticity / atrial natriuretic peptide / fetal gene / sino-atrial node / developmental change |
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| Research Abstract |
We have investigated the presence of resident heart cells that are distinct from cardiomyocytes in adult mice. The heart was coronary perfused with enzymes and both ventricles were excised and further digested. After spinning the ventricular myocytes down, the supernatant fraction (cardiac myocyte-depleted fraction, CMDF) was cultured in methylcellulose-based semisolid culture medium. Three to five days after plating, some of the small cells adhered to the bottom of the dishes gradually developed their shapes and started beating spontaneously. These cells were mostly multinucleated, well sarcomeric-organized and expressed cardiac specific proteins, defined as a novel type of heart cells, atypically-shaped cardiomyocytes (ACMs). The cell population of ACMs was highest at neonatal period and significantly decreased within the first 5 weeks and reached a plateau in the adult stage. The ACMs obtained from both newborn and aged mice express the fetal cardiac gene products, such as atrial natriuretic peptide (ANP) and voltage-gated Ca2+channel CaV3.2. We examined whether CMDF cells, including ACMs, that underwent simulated lethal ischemia could develop into beating cells. When CMDF cells pre-exposed to ischemia were cultured for 6 days, the cell number of beating ACMs was ~50% of normoxic preparations. Electron microscopic analyses of ACMs displayed constitutively active autophagy during the culture even in the normoxic conditions. The results suggest the possibility that the development of beating ACMs could occur in injured heart, even if the surviving cell population is small.
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