Document Detail

Hyperpolarization-activated cyclic nucleotide-modulated 'HCN' channels confer regular and faster rhythmicity to beating mouse embryonic stem cells.
MedLine Citation:
PMID:  18033814     Owner:  NLM     Status:  MEDLINE    
The hyperpolarization-activated cation current (I(f)), and the hyperpolarization-activated cyclic nucleotide-modulated 'HCN' subunits that underlie it, are important components of spontaneous activity in the embryonic mouse heart, but whether they contribute to this activity in mouse embryonic stem cell-derived cardiomyocytes has not been investigated. We address this issue in spontaneously beating cells derived from mouse embryonic stem cells (mESCs) over the course of development in culture. I(f) and action potentials were recorded from single beating cells at early, intermediate and late development stages using perforated whole-cell voltage- and current-clamp techniques. Our data show that the proportion of cells expressing I(f), and the density of I(f) in these cells, increased during development and correlated with action potential frequency and the rate of diastolic depolarization. The I(f) blocker ZD7288 (0.3 microm) reduced I(f) and the beating rate of embryoid bodies. Taken together, the activation kinetics of I(f) and results from Western blots are consistent with the presence of the HCN2 and HCN3 isoforms. At all stages of development, isoproterenol (isoprenaline) and acetylcholine shifted the voltage dependence of I(f) to more positive and negative voltages, respectively, and they also increased and decreased the beating rate of embryonic cell bodies, respectively. Together, the data suggest that current through HCN2 and HCN3 channels confers regular and faster rhythmicity to mESCs, which mirrors the developing embryonic mouse heart, and contributes to modulation of rhythmicity by autonomic stimulation.
Yang Qu; Gina M Whitaker; Leif Hove-Madsen; Glen F Tibbits; Eric A Accili
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-11-22
Journal Detail:
Title:  The Journal of physiology     Volume:  586     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-04     Completed Date:  2008-06-23     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  701-16     Citation Subset:  IM    
Cardiac Membrane Research Laboratory, Simon Fraser University, Burnaby, BC, Canada.
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MeSH Terms
Acetylcholine / pharmacology
Action Potentials / physiology*
Cardiac Electrophysiology
Cardiotonic Agents / pharmacology
Cell Line
Cholinergic Agents / pharmacology
Cyclic Nucleotide-Gated Cation Channels / metabolism*
Embryonic Stem Cells / cytology,  drug effects,  metabolism*
Heart / embryology*,  physiology
Heart Rate / physiology*
Ion Channels / metabolism*
Isoproterenol / pharmacology
Myocardial Contraction / physiology
Myocardium / cytology
Myocytes, Cardiac / cytology,  drug effects,  metabolism
Patch-Clamp Techniques
Protein Isoforms / metabolism
Reg. No./Substance:
0/Cardiotonic Agents; 0/Cholinergic Agents; 0/Cyclic Nucleotide-Gated Cation Channels; 0/HCN2 potassium channel; 0/HCN3 protein, mouse; 0/Ion Channels; 0/Protein Isoforms; 51-84-3/Acetylcholine; 7683-59-2/Isoproterenol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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