ArticleThe Journal of clinical investigation2010
Limited forward trafficking of connexin 43 reduces cell-cell coupling in stressed human and mouse myocardium.
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.
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Who cites it
165 citing papers in PubMed, 244 citations in OpenAlex.
- The effects of polyunsaturated fatty acids and antioxidant vitamins on atrial oxidative stress, nitrotyrosine residues, and connexins following extracorporeal circulation in patients undergoing cardiac surgery.Molecular and cellular biochemistry · 2017Trial
- Optoelectronic Biohybrid Platform Enables Light-Controlled Cardiac Structural and Functional Feedback.Cell biomaterials · 2026Article
- Vasohibin 1 acts as a key regulator of arrhythmogenesis in pressure-overload-induced cardiac hypertrophy.Acta pharmacologica Sinica · 2026Article
- Propafenone-mediated gap junctional uncoupling results from aberrant connexin-43 trafficking.Pharmacological reports : PR · 2026Article
- Perioperative atrial fibrillation after non-cardiac surgery - A narrative review.Clinical research in cardiology : official journal of the German Cardiac Society · 2026Review
- Review
- Spastin-mediated severing of glutamylated microtubules controls cardiomyocyte coupling.Nature cardiovascular research · 2026Article
- The roles of the microtubule cytoskeletal network in cardiac mechanobiology.Journal of cell science · 2026Review
- Hydrogen peroxide reduces Cx40, Cx43, and Cx45 gap junction function.Cell and tissue research · 2026Article
- Inhibition of Pyk2 prevents Cx43 remodeling and cardiomyocyte injury during hypoxic and adrenergic stress.Journal of molecular and cellular cardiology · 2026Article
- Article
- Cardiac alterations induced by Trypanosoma cruzi extracellular vesicles and immune complexes.PLoS neglected tropical diseases · 2025Article
- Review
- A truncated isoform of Connexin43 caps actin to organize forward delivery of full-length Connexin43.The Journal of cell biology · 2025Article
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Article
- The activation of P38MAPK Signaling Pathway Impedes the Delivery of the Cx43 to the Intercalated Discs During Cardiac Ischemia-Reperfusion Injury.Journal of cardiovascular translational research · 2024Article
- Innate and adaptive immunity in acute myocarditis.International journal of cardiology · 2024Review
- Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis.Circulation research · 2024Article
- The Role ofCirculation research · 2024Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
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.
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Registered trials
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.