Document Type

Journal Article

Department/Unit

School of Chinese Medicine

Title

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

Language

English

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/G 1 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. © 2010 Springer-Verlag.

Keywords

Cell cycle, Excitability, Hyperpolarization-activated channels, Ion channels, Stem cell

Publication Date

2011

Source Publication Title

Pflügers Archiv European Journal of Physiology

Volume

461

Issue

1

Start Page

191

End Page

202

Publisher

Springer Verlag

DOI

10.1007/s00424-010-0899-9

Link to Publisher's Edition

http://dx.doi.org/10.1007/s00424-010-0899-9

ISSN (print)

00316768

ISSN (electronic)

14322013

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