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Pflügers Archiv - European Journal of Physiology

, Volume 461, Issue 1, pp 191–202 | Cite as

Effects of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers on the proliferation and cell cycle progression of embryonic stem cells

  • Yuen-Ting Lau
  • Chun-Kit Wong
  • Jialie Luo
  • Lok-Hang Leung
  • Pui-Fong Tsang
  • Zhao-Xiang Bian
  • Suk-Ying Tsang
Signaling and Cell Physiology

Abstract

Embryonic stem cells (ESCs) can uniquely proliferate indefinitely and differentiate into all cell lineages. ESCs may therefore provide an unlimited supply of cells for cell-based therapies. Previous study reported the presence of hyperpolarization-activated inward currents in undifferentiated mouse (m) ESCs, but the functional role of this hyperpolarization-activated current in mESCs is unknown. In this study, the role of this current in maintaining the proliferative capacity and the cell cycle progression of ESCs was investigated. In D3 mESCs, this hyperpolarization-activated inward current can be blocked by HCN channel blocker ZD7288. Application of the HCN channel blockers, cesium (1–10 mM) or ZD7288 (0.1–30 μM), attenuated cell proliferation in a concentration-dependent manner. Both HCN blockers were found to be non-cytotoxic to mESCs as determined by cell viability test. Interestingly, ZD7288 at 10 and 30 μM was found to decrease the proportion of cells in G0/G1 phase and increase the proportion of cells in S phase. This suggests that this hyperpolarization-activated current can affect the cell cycle progression in mESCs. In summary, the present investigation suggests that ESC proliferation and cell cycle progression can be regulated by this hyperpolarization-activated current.

Keywords

Ion channels Hyperpolarization-activated channels Stem cell Cell cycle Excitability 

Abbreviations

ESCs

Embryonic stem cells

HCN channel

Hyperpolarization-activated cyclic nucleotide-gated channel

TBP

TATA-box binding protein

Notes

Acknowledgements

This study was supported by the Direct Grant for Research from the Chinese University of Hong Kong (CUHK) and the Lee Hysan Foundation Research Grant. Y.T.L. and C.K.W. were supported by postgraduate studentships from the CUHK. We would like to thank Ms Cecilia Sze-Lee Leung and Dr. Winnie Poon for their excellent technical support.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Yuen-Ting Lau
    • 1
    • 6
  • Chun-Kit Wong
    • 1
  • Jialie Luo
    • 7
  • Lok-Hang Leung
    • 8
  • Pui-Fong Tsang
    • 1
  • Zhao-Xiang Bian
    • 7
  • Suk-Ying Tsang
    • 1
    • 2
    • 3
    • 4
    • 5
    • 9
  1. 1.Biochemistry Program, School of Life SciencesChinese University of Hong KongHong KongChina
  2. 2.Cell and Molecular Biology Program, School of Life SciencesChinese University of Hong KongHong KongChina
  3. 3.State Key Laboratory of AgrobiotechnologyChinese University of Hong KongHong KongChina
  4. 4.Stem Cell and Regeneration Program, School of Biomedical SciencesChinese University of Hong KongHong KongChina
  5. 5.Key Laboratory for Regenerative Medicine, Ministry of EducationChinese University of Hong KongHong KongChina
  6. 6.Molecular Biotechnology Program, School of Life SciencesChinese University of Hong KongHong KongChina
  7. 7.School of Chinese MedicineHong Kong Baptist UniversityHong KongChina
  8. 8.Faculty of MedicineChinese University of Hong KongHong KongChina
  9. 9.School of Life SciencesChinese University of Hong KongHong KongChina

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