Evidence map›Paper›PMID 34440870›Full record

ArticleCells2021

Flecainide Paradoxically Activates Cardiac Ryanodine Receptor Channels under Low Activity Conditions: A Potential Pro-Arrhythmic Action.

Samantha C Salvage, Esther M Gallant, James A Fraser, Christopher L-H Huang, Angela F Dulhunty

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
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

14 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. FKBP12 binds to the cardiac ryanodine receptor with negative cooperativity: implications for heart muscle physiology in health and disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Article
  8. Feedback contributions to excitation-contraction coupling in native functioning striated muscle.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  9. Article
  10. Article
  11. How does flecainide impact RyR2 channel function?The Journal of general physiology · 2022
    Article
  12. Article
  13. Review
  14. 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 at 2 institutions in 2 countries.

Samantha C SalvagePhysiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.ORCID 0000-0002-5793-2349
Esther M GallantEccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, 131 Garran Road, Acton 2601, Australia.
James A FraserPhysiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.ORCID 0000-0002-6505-1883
Christopher L-H HuangPhysiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.ORCID 0000-0001-9553-6112
Angela F DulhuntyEccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, 131 Garran Road, Acton 2601, Australia.
University of Cambridge · GBAustralian National University · AU

Funding

Biotechnology and Biological Sciences Research Council BB/F023863/1British Heart Foundation PG/14/79/31102British Heart Foundation PG/15/12/31280British Heart Foundation PG/19/59/34582Medical Research Council MR/M001288/1National Health and Medical Research Council APP108477Wellcome Trust 105727/Z/14/Z
6 · The paper itself

Abstract

Cardiac ryanodine receptor (RyR2) mutations are implicated in the potentially fatal catecholaminergic polymorphic ventricular tachycardia (CPVT) and in atrial fibrillation. CPVT has been successfully treated with flecainide monotherapy, with occasional notable exceptions. Reported actions of flecainide on cardiac sodium currents from mice carrying the pro-arrhythmic homozygotic RyR2-P2328S mutation prompted our explorations of the effects of flecainide on their RyR2 channels. Lipid bilayer electrophysiology techniques demonstrated a novel, paradoxical increase in RyR2 activity. Preceding flecainide exposure, channels were mildly activated by 1 mM luminal Ca

Indexed as

AnimalsAnti-Arrhythmia AgentsArrhythmias, CardiacCalciumFlecainideIon Channel GatingLipid BilayersMembrane PotentialsMiceRyanodine Receptor Calcium Release ChannelSarcoplasmic ReticulumVoltage-Gated Sodium Channel BlockersAnti-Arrhythmia AgentsCalciumFlecainideLipid Bilayersryanodine receptor 2. mouseRyanodine Receptor Calcium Release ChannelVoltage-Gated Sodium Channel Blockersatrial fibrillationcatecholaminergic polymorphic ventricular tachycardiaflecainideRyR2RyR2 activationRyR2 inhibitionRyR2-P2328S

Identifiers

PMID34440870
PMCPMC8394964
OpenAlexW3196009408

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.