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Electrophysiological properties of cardiomyocytes differentiated from mouse embrionic stem cells

Research Project

Project/Area Number 15590775
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNippon 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
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsstem cells / ion channels / Na / K ATPase / Ca exchanger / cardiomyocvtes / K ATPase / 胚性幹細胞 / カルシウム / IP_3レセプター / Ca電流
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.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report

Research Products

(4 results)

All 2005 2004 Other

All Journal Article (3 results) Publications (1 results)

  • [Journal Article] Na/K ATPase and its functional coupling with Na/Ca exchanger in mouse embryonic stem cells during differentiation into cardio-myocytes.2005

    • Author(s)
      Otsu K, Kuruma A, Yanagida E, Shoji S, Inoue T, Hirayama Y, et al.
    • Journal Title

      Cell Calcium 37

      Pages: 137-151

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Na/K ATPase and its functional coupling with Na/Ca exchanger in mouse embryonic stem cells during differentiation into cardiomyocytes2005

    • Author(s)
      Otsu K, Kuruma A, Yanagida E, Shoji S, Inoue T, Hirayama Y, et al.
    • Journal Title

      Cell Calcium 37

      Pages: 137-151

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ca2+ signaling pathways in mouse embryonic stem cells2004

    • Author(s)
      Yanagida E, Otsu Y, Hirayama Y, Shoji H, Uematsu M, Hiraoka M, Kawano S.
    • Journal Title

      Cell Calcium 36

      Pages: 135-146

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Yanagida E, Shoji S, Hirayama Y, et al.: "Functional expression of Ca^<2+> signaling pathways in mouse embryonic stem cells."Cell Calcium. in prress. (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-03-31   Modified: 2016-04-21  

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