Project/Area Number |
07407073
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Nagoya University |
Principal Investigator |
TOYAMA Junji Nagoya Univ.Res.Inst.of Environ.Med., Professor, 環境医学研究所, 教授 (20023658)
|
Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Kiyoko Seinan Gakuin Univ.Dept.of Literature, Professor, 文学部, 教授 (20192396)
KAMIYA Kaichiro Nagoya Univ.Res.Inst.of Environ.Med., Assistant, 環境医学研究所, 助手 (50194973)
KODAMA Itsuo Nagoya Univ.Res.Inst.of Environ.Med., Professor, 環境医学研究所, 教授 (30124720)
YAMAMURA Hideki Nagoya Univ.Res.Inst.of Environ.Med., Professor, 環境医学研究所, 教授 (40034003)
|
Project Period (FY) |
1995 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Keywords | cultured cardiomyocytes / ion channels / growth factor / differentiation / mesoderm / commitment / 中胚葉イオンチャネル / 分化 / コミットメント / 成長因子 / 培養心筋 |
Research Abstract |
This study was aimed to investigate terminal differentiaiotn of cardiac progenitor cells in the early embryogenesis, and ionic currents development after birth in relation to exogenous influence. We heve already established culture systems of the mouse gastrula mesoderm and rat neonatal ventricular myocytes. Our study in early cardiogenesis indicates that at 7.5 days post coitum, when gastrulation is completed, mesodermal cardiac progenitor cells commit to autonomous differentiation into contractile cardiomyocytes, while 7.25 day post coitum mesoderm requires additional signaling for terminal differentiation. Insulin, insulin-like growth factor and platelet derived growth factor induced cardiomyocytes with spontaneous beating. In ionic current analysis of neonatal rat ventricular myocytes cultured for 5-15 days, development of ionic currents, especially of I_<to>, showed various patterns, which were dependent on culture states. Hypoxic culture condition retarded or dedifferentiated I_<to> development. Basic fibroblast growth factor enhanced development of I_<to>. Insulin-like growth factor increased the percentage of cells expressing I_<Kur>. In order to explore the molecular mechanism of developmental changes in ionic currents induced by culture condition, we are engaged in microinjection of the exogenous mRNA into cultured cardiomyocytes. The changes of culture condition, such as hypoxia and modification of culture medium, regulated the ion channels expression. Our findings suggest that environmental factors play important role in ionic channels development as well as in the early cardiogenesis.
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