Evidence map›Paper›PMID 41766039›Full record

ArticlePharmacological reports : PR2026

Propafenone-mediated gap junctional uncoupling results from aberrant connexin-43 trafficking.

Encan Li, Najla Boujeddaine, Britt Mol, Emmy Penning de Vries, Marcel A G van der Heyden

Abstract read
In one paragraph

Article in Pharmacological reports : PR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Encan LiDepartment of Pharmacy, Tianjin First Central Hospital, Tianjin, China.ORCID http://orcid.org/0000-0002-2741-2289
Najla BoujeddaineDepartment of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
Britt MolDepartment of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
Emmy Penning de VriesDepartment of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
Marcel A G van der HeydenDepartment of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands. m.a.g.vanderheyden@umcutrecht.nl.ORCID http://orcid.org/0000-0002-4225-7942

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundConnexin-43 (Cx43) is the principal gap junction protein in the heart, mediating electrical coupling and ion exchange between cardiomyocytes to maintain synchronous contraction. Any disruption or malfunction of Cx43 can lead to arrhythmias and other cardiac issues. Understanding the functions and regulation of Cx43 is vital in both basic research and clinical contexts. Propafenone, a class Ic antiarrhythmic drug, has shown promise in rhythm control; however, its precise impact on cardiac cellular physiology, particularly regarding Cx43, remains incompletely understood. The present study investigated propafenone’s effects on Cx43 protein content, physiology, and underlying mechanisms in cell systems.

methodsCell lines include human embryonic kidney HEK293 cells transfected with Cx43 (Ex-HEK); differentiated murine embryonic carcinoma EPI7 cells with an epithelioid morphology and visceral endoderm-like END2 cells, both endogenously expressing functional Cx43. Cx43 protein contents were determined by Western blot analysis, whereas immunofluorescence (IF) imaging was used to assess the subcellular localization of Cx43 proteins. Dye injections were used to gain insight into the effects of propafenone on Cx43 function.

resultsFull-length Cx43 protein levels were dose-dependently increased after propafenone treatment and IF microscopy showed an intracellular accumulation of Cx43 protein, both on heterologously and endogenously expressed Cx43. Propafenone did not alter the Cx43 half-life, in contrast to the lysosomal inhibitor chloroquine. Finally, gap-junctional coupling was decreased by chronic propafenone treatment.

conclusionWe conclude that propafenone increases non-functional Cx43 protein content, resulting in its intracellular accumulation, as a side effect.

Indexed as

Anti-Arrhythmia AgentsConnexin 43Gap JunctionsPropafenoneAnimalsCell LineDose-Response Relationship, DrugHEK293 CellsHumansMiceProtein TransportAnti-Arrhythmia AgentsConnexin 43GJA1 protein, humanPropafenoneAccumulationCx43Metabolic couplingPropafenoneTrafficking

Identifiers

PMID41766039
PMCPMC13275528

What Socratic holds

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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 Socratic graph.