Evidence map›Paper›PMID 20038810›Full record

ArticleThe Journal of clinical investigation2010

Limited forward trafficking of connexin 43 reduces cell-cell coupling in stressed human and mouse myocardium.

James W Smyth, Ting-Ting Hong, Danchen Gao, Jacob M Vogan, Brian C Jensen, Tina S Fong, Paul C Simpson, Didier Y R Stainier, Neil C Chi, Robin M Shaw

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.

0numbers the graph read from it
0cells of the map it votes in
165citing papers in PubMed
8.9field-weighted citation impact, top 1% 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

165 citing papers in PubMed, 244 citations in OpenAlex.

  1. Trial
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  5. Perioperative atrial fibrillation after non-cardiac surgery - A narrative review.Clinical research in cardiology : official journal of the German Cardiac Society · 2026
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  18. Innate and adaptive immunity in acute myocarditis.International journal of cardiology · 2024
    Review
  19. Article
  20. The Role ofCirculation research · 2024
    Article

105 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

James W SmythCardiovascular Research Institute, Department of Medicine, University of California-San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA.
Ting-Ting Hong
Danchen Gao
Jacob M Vogan
Brian C Jensen
Tina S Fong
Paul C Simpson
Didier Y R Stainier
Neil C Chi
Robin M Shaw
University of California, San Francisco · USSan Francisco VA Medical Center · US

Funding

CATECHOLAMINES AND HYPERTROPHY OF CULTURED HEART CELLSR01HL031113 · NHLBI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI SIMPSON, PAUL C · 1985 to 2021
$5.7M
MOLECULAR GENETICS OF CARDIAC CELL DIFFERENTIATIONR01HL054737 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COUGHLIN, SHAUN R. · 1996 to 2015
$5.4M
Novel Mechanisms of Cardiac Ion Channel RegulationR01HL094414 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHAW, ROBIN M · 2009 to 2018
$3.6M
Alpha-1-Adrenergic Receptor Subtypes in the Cells of the Human HeartK08HL096836 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JENSEN, BRIAN C · 2009 to 2013
$663k
Excitability Between Cardiac and Non-Cardiac CellsK08HL075449 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHAW, ROBIN M · 2005 to 2009
$607k
NHLBI NIH HHS HL075449NHLBI NIH HHS HL094414NHLBI NIH HHS HL31113NHLBI NIH HHS HL54737NHLBI NIH HHS K08 HL075449NHLBI NIH HHS K08 HL096836NHLBI NIH HHS R01 HL031113NHLBI NIH HHS R01 HL054737NHLBI NIH HHS R01 HL094414
6 · The paper itself

Abstract

Gap junctions form electrical conduits between adjacent myocardial cells, permitting rapid spatial passage of the excitation current essential to each heartbeat. Arrhythmogenic decreases in gap junction coupling are a characteristic of stressed, failing, and aging myocardium, but the mechanisms of decreased coupling are poorly understood. We previously found that microtubules bearing gap junction hemichannels (connexons) can deliver their cargo directly to adherens junctions. The specificity of this delivery requires the microtubule plus-end tracking protein EB1. We performed this study to investigate the hypothesis that the oxidative stress that accompanies acute and chronic ischemic disease perturbs connexon forward trafficking. We found that EB1 was displaced in ischemic human hearts, stressed mouse hearts, and isolated cells subjected to oxidative stress. As a result, we observed limited microtubule interaction with adherens junctions at intercalated discs and reduced connexon delivery and gap junction coupling. A point mutation within the tubulin-binding domain of EB1 reproduced EB1 displacement and diminished connexon delivery, confirming that EB1 displacement can limit gap junction coupling. In zebrafish hearts, oxidative stress also reduced the membrane localization of connexin and slowed the spatial spread of excitation. We anticipate that protecting the microtubule-based forward delivery apparatus of connexons could improve cell-cell coupling and reduce ischemia-related cardiac arrhythmias.

Indexed as

AnimalsCell CommunicationCell MembraneConnexin 43FemaleGap JunctionsHeLa CellsHumansMaleMiceMice, Inbred BALB CMice, Inbred C57BLMicrotubule-Associated ProteinsMicrotubulesMyocardial IschemiaMyocardiumConnexin 43MAPRE1 protein, humanMicrotubule-Associated Proteins

Identifiers

PMID20038810
PMCPMC2798685
OpenAlexW2031426329

What OpenQuestion holds

Textmetadata
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.