2004 Fiscal Year Final Research Report Summary
Electrophysiological properties of cardiomyocytes differentiated from mouse embrionic stem cells
Project/Area Number |
15590775
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
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Research Institution | Nippon Medical School |
Principal Investigator |
HIRAYAMA Yoshiyuki Nippon Medical School, Department of Medicine, Research Assistant, 医学部, 助手 (50322516)
|
Co-Investigator(Kenkyū-buntansha) |
KAWANO Seiko Tokyo Medical & Dental University, Associated Professor, 医学部, 助教授 (00177718)
|
Project Period (FY) |
2003 – 2004
|
Keywords | stem cells / ion channels / Na / K ATPase / Na / Ca exchanger / cardiomyocvtes |
Research Abstract |
Cardiomyocytes derived from mouse embryonic stem cells(mES) cells exhibit expression of ion channels and several signal transduction systems during their differentiation. Na/K ATPase and Na/Ca exchange play an important role to keep homeostasis in cardiac cells during excitation in cardiomyocytes. But these expression mechanisms of the ion transporter or exchanger have not been well clarified. In this project we examined the functional expression of this transporter and exchanger in mES cells during differentiation into cardiac myocytes. We showed that an ouabain-high sensitive Na/K ATPase was expressed and functioned even in the undifferentiated mES cells but the activity of Na/K ATPase increased during the differentiation into cardiac myocytes. We detected the expressions of mRNA for α1- and α3-subunit of the Na/K ATPase in mES cell and cardiomyocytes derived from mES cells by using RT-PCR. But we could detect mRNA for α2-subuniit only in cardiomyocytes differentiated from mES cells. We detected mRNA for the Na/Ca exchanger 1 isoform(NCX1) in mES cells and the expression levels of this exchanger gradually increased throughout the differentiation into cardiomyocytes. More than 75 % of derived cardiomyocytes showed intracellular Ca^<2+> oscillation when we inhibited Na/K ATPase at the middle stage of differentiation (10-day induction from mES cells). This result suggests the functional coupling with NCX1 and Na/K ATPase at the middle stages of differentiation of cardiocmyocytes from mES ells. We conclude that α2-subunit of Na/K ATPase contiributes to the functional coupling with NCX1 at the middle stage of cardiac differentiation from mES cells.
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Research Products
(2 results)