Changes of HCN gene expression and If currents in Nkx2.5-positive cardiomyocytes derived from murine embryonic stem cells during differentiation

  • Yano Shuichi
    Department of Cardiovascular Medicine, Tottori University Faculty of Medicine
  • Miake Junichiro
    Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
  • Mizuta Einosuke
    Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
  • Manabe Kasumi
    Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
  • Bahrudin Udin
    Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
  • Morikawa Kumi
    Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
  • Arakawa Keita
    Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
  • Sasaki Norihito
    Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
  • Igawa Osamu
    Department of Cardiovascular Medicine, Tottori University Faculty of Medicine
  • Shigemasa Chiaki
    Department of Cardiovascular Medicine, Tottori University Faculty of Medicine
  • Yamamoto Yasutaka
    Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
  • Morisaki Takayuki
    Department of Bioscience, National Cardiovascular Center Research Institute
  • Hidaka Kyoko
    Department of Bioscience, National Cardiovascular Center Research Institute
  • Kurata Yasutaka
    Department of Physiology, Kanazawa Medical College
  • Yoshida Akio
    Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
  • Shiota Goshi
    Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science
  • Higaki Katsumi
    Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University
  • Ninomiya Haruaki
    Department of Biological Regulation, Tottori University Faculty of Medicine
  • Lee Jong-Kook
    Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University
  • Shirayoshi Yasuaki
    Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
  • Hisatome Ichiro
    Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science

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抄録

Changes in the expression of hyperpolarization-activated cyclic nucleotide (HCN)-gated channels and If currents during the differentiation of embryonic stem cells into cardiac cells remain unknown. We examined changes of HCN genes in expression and function during the differentiation of Nkx2.5-positive cardiac precursor cells derived from mouse ES cells using cell sorting, RTPCR, immunofluorescence and whole cell patch-clamp techniques. Cs+-induced inhibition of automaticity and transcription of HCN genes increased during differentiation. Expressions of Nkx2.5, a marker of cardiac progenitor cell, and Flk1, a marker of hemangioblast, were mutually exclusive. Messenger RNA and proteins encoded by HCN1 and 4 genes were predominantly observed in Nkx2.5-positive cells on day 15, although Flk1-positive cells did not express genes of the HCN family on that day. Cs+-induced prolongation of the cycle of spontaneous action potentials and If currents were predominantly observed on day 15. These results suggested that a fraction of Nkx2.5-positive cardiac precursor cells was committed to pacemaking cells expressing If channels predominantly encoded by HCN 1 and 4 genes.

収録刊行物

  • Biomedical Research

    Biomedical Research 29 (4), 195-203, 2008

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