Evidence map›Paper›PMID 18033814›Full record

ArticleThe Journal of physiology2008

Hyperpolarization-activated cyclic nucleotide-modulated 'HCN' channels confer regular and faster rhythmicity to beating mouse embryonic stem cells.

Yang Qu, Gina M Whitaker, Leif Hove-Madsen, Glen F Tibbits, Eric A Accili

Abstract read
In one paragraph

Article in The Journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. HCN2 Channel-Induced Rescue of Brain TeratogenesisFrontiers in cellular neuroscience · 2020
    Article
  5. Article
  6. Article
  7. TheFrontiers in molecular neuroscience · 2017
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. SK4 Ca2+ activated K+ channel is a critical player in cardiac pacemaker derived from human embryonic stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2013
    Article
  16. Article
  17. The beginning of the calcium transient in rat embryonic heart.The journal of physiological sciences : JPS · 2011
    Article
  18. Article
  19. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Yang QuCardiac Membrane Research Laboratory, Simon Fraser University, Burnaby, BC, Canada.
Gina M Whitaker
Leif Hove-Madsen
Glen F Tibbits
Eric A Accili

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

AcetylcholineAction PotentialsAnimalsCardiac ElectrophysiologyCardiotonic AgentsCell LineCholinergic AgentsCyclic Nucleotide-Gated Cation ChannelsEmbryonic Stem CellsHeartHeart RateHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsIon ChannelsIsoproterenolMiceMyocardial ContractionAcetylcholineCardiotonic AgentsCholinergic AgentsCyclic Nucleotide-Gated Cation ChannelsHcn2 protein, mouseHCN3 protein, mouseHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsIon ChannelsIsoproterenolPotassium ChannelsProtein Isoforms

Identifiers

PMID18033814
PMCPMC2375615

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.