Evidence map›Paper›PMID 26503720›Full record

ArticleThe Journal of general physiology2015

Altered conductance and permeability of Cx40 mutations associated with atrial fibrillation.

Ana Santa Cruz, Gülistan Meşe, Laima Valiuniene, Peter R Brink, Thomas W White, Virginijus Valiunas

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of general physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

17 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Therapeutic advances in atrial fibrillation based on animal models.Journal of Zhejiang University. Science. B · 2024
    Review
  3. Article
  4. Review
  5. Article
  6. Mechanisms of Connexin Regulating Peptides.International journal of molecular sciences · 2021
    Review
  7. Review
  8. Article
  9. Overview of the Components of Cardiac Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2019
    Review
  10. Electrical coupling and its channels.The Journal of general physiology · 2018
    Review
  11. Article
  12. Article
  13. Article
  14. Connexins and Pannexins in Vascular Function and Disease.International journal of molecular sciences · 2018
    Review
  15. Article
  16. Regulation of cardiac gap junctions by protein phosphatases.Journal of molecular and cellular cardiology · 2017
    Review
  17. Article
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

6 authors at 1 institution in 1 country.

Ana Santa CruzDepartment of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11792.
Gülistan MeşeDepartment of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11792.
Laima ValiunieneDepartment of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11792.
Peter R BrinkDepartment of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11792.
Thomas W WhiteDepartment of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11792.
Virginijus ValiunasDepartment of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11792 virginijus.valiunas@stonybrook.edu.
Stony Brook University · US

Funding

MicroRNA permeability of connexin mutants related to genetic diseaseR01GM088181 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI VALIUNAS, VIRGINIJUS · 2011 to 2020
$2.8M
Cx26 mutations in syndromic deafness linked to skin diseaseR01AR059505 · NIAMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI WHITE, THOMAS W · 2010 to 2014
$1.7M
SiRNA therapeutics: Gap junction delivery in vitro and in vivoR01GM088180 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI BRINK, PETER R, COHEN, IRA S · 2010 to 2013
$1.6M
NIAMS NIH HHS AR59505NIAMS NIH HHS R01 AR059505NIGMS NIH HHS GM088181NIGMS NIH HHS GM88180NIGMS NIH HHS R01 GM088180NIGMS NIH HHS R01 GM088181
6 · The paper itself

Abstract

Gap junctions ensure the rapid propagation of the action potential throughout the myocardium. Three mutant forms of connexin40 (Cx40; A96S, M163V, and G38D), the primary component of the atrial gap junction channel, are associated with atrial fibrillation and retain the ability to form functional channels. We determined the biophysical properties of these mutant gap junctions in transiently transfected HeLa and N2A cells. All three mutants showed macroscopic junctional conductances over the range of 0.5 to 40 nS, and voltage dependences comparable to those of wild-type (WT) Cx40. However, the unitary conductance of G38D channels was ∼1.6-fold higher than that of WT Cx40 channels (∼220 vs. ∼135 pS), whereas the unitary conductances of the A96S and M163V mutants were similar to that of WT Cx40. Furthermore, the M163V and G38D channels exhibited approximately two- and approximately fivefold higher permeability to the anionic dye Lucifer yellow (LY) relative to K+ (LY/K+) compared with that of WT Cx40, whereas A96S LY transfer was similar to that of WT (G38D > M163V > A96S ≈ Cx40WT). In contrast, G38D channels were almost impermeable to cationic ethidium bromide (EtBr), suggesting that G38D alters channel selectivity. Conversely, A96S and M163V channels showed enhanced EtBr permeability relative to WT Cx40, with the following permeability order: M163V > A96S > Cx40WT > G38D. Altered conductive and permeability properties of mutant channels suggest an essential role for Cx40-mediated biochemical and electrical coupling in cardiac tissues. The altered properties of the three single-base substitution mutants may play a role in mechanisms of reentry arrhythmias.

Indexed as

Mutation, MissenseAnimalsAtrial FibrillationConnexinsGap Junction alpha-5 ProteinHeLa CellsHumansIon TransportMicePermeabilityPotassiumConnexinsGap Junction alpha-5 ProteinPotassium

Identifiers

PMID26503720
PMCPMC4621748
OpenAlexW2261163335

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.