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Effects of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers on the proliferation and cell cycle progression of embryonic stem cells.
MedLine Citation:
PMID:  21110038     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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 G(0)/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.
Authors:
Yuen-Ting Lau; Chun-Kit Wong; Jialie Luo; Lok-Hang Leung; Pui-Fong Tsang; Zhao-Xiang Bian; Suk-Ying Tsang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-26
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  461     ISSN:  1432-2013     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  191-202     Citation Subset:  IM    
Affiliation:
Biochemistry Program, School of Life Sciences, Chinese University of Hong Kong, Hong Kong, China.
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