Evidence map›Paper›PMID 24733048›Full record

ArticlePloS one2014

Atrial fibrillation-linked germline GJA5/connexin40 mutants showed an increased hemichannel function.

Yiguo Sun, Matthew D Hills, Willy G Ye, Xiaoling Tong, Donglin Bai

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

15 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Connexin Mutations and Hereditary Diseases.International journal of molecular sciences · 2022
    Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Genetics and Epigenetics of Atrial Fibrillation.International journal of molecular sciences · 2020
    Review
  8. Observational
  9. Article
  10. Article
  11. Review
  12. TheClinical science (London, England : 1979) · 2018
    Article
  13. Review
  14. Article
  15. Diseases associated with leaky hemichannels.Frontiers in cellular neuroscience · 2015
    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 1 institution in 1 country.

Yiguo SunDepartment of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
Matthew D HillsDepartment of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
Willy G YeDepartment of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
Xiaoling TongDepartment of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
Donglin BaiDepartment of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
Western University · CA

Funding

Canadian Institutes of Health Research MOP86649
6 · The paper itself

Abstract

Mutations in GJA5 encoding the gap junction protein connexin40 (Cx40) have been linked to lone atrial fibrillation. Some of these mutants result in impaired gap junction function due to either abnormal connexin localization or impaired gap junction channels, which may play a role in promoting atrial fibrillation. However, the effects of the atrial fibrillation-linked Cx40 mutants on hemichannel function have not been studied. Here we investigated two atrial fibrillation-linked germline Cx40 mutants, V85I and L221I. These two mutants formed putative gap junction plaques at cell-cell interfaces, with similar gap junction coupling conductance as that of wild-type Cx40. Connexin deficient HeLa cells expressing either one of these two mutants displayed prominent propidium iodide-uptake distinct from cells expressing wild-type Cx40 or other atrial fibrillation-linked Cx40 mutants, I75F, L229M, and Q49X. Propidium iodide-uptake was sensitive to [Ca2+]o and the hemichannel blockers, carbenoxolone, flufenamic acid and mefloquine, but was not affected by the pannexin 1 channel blocking agent, probenecid, indicating that uptake is most likely mediated via connexin hemichannels. A gain-of-hemichannel function in these two atrial fibrillation-linked Cx40 mutants may provide a novel mechanism underlying the etiology of atrial fibrillation.

Indexed as

AnimalsAtrial FibrillationCalciumCarbenoxoloneCations, DivalentConnexinsGap Junction alpha-5 ProteinGap JunctionsGerm CellsHeLa CellsHumansMiceMutant ProteinsMutationPatch-Clamp TechniquesPropidiumCalciumCarbenoxoloneCations, DivalentConnexinsGap Junction alpha-5 ProteinMutant ProteinsPropidiumRecombinant Fusion Proteins

Identifiers

PMID24733048
PMCPMC3986259
OpenAlexW1989449524

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.