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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.
- Source :
-
Pflugers Archiv : European journal of physiology [Pflugers Arch] 2011 Jan; Vol. 461 (1), pp. 191-202. Date of Electronic Publication: 2010 Nov 26. - Publication Year :
- 2011
-
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 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.
- Subjects :
- Animals
Cell Survival drug effects
Cesium pharmacology
Cyclic Nucleotide-Gated Cation Channels metabolism
Cyclin B biosynthesis
Embryonic Stem Cells drug effects
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Membrane Potentials
Mice
Patch-Clamp Techniques
Pyrimidines pharmacology
Cell Cycle drug effects
Cell Proliferation drug effects
Cyclic Nucleotide-Gated Cation Channels antagonists & inhibitors
Embryonic Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-2013
- Volume :
- 461
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Pflugers Archiv : European journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 21110038
- Full Text :
- https://doi.org/10.1007/s00424-010-0899-9