ArticleHeart rhythm2012
Remodeling of mechanical junctions and of microtubule-associated proteins accompany cardiac connexin43 lateralization.
Article in Heart rhythm, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 68 citations in OpenAlex.
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- Overexpression of Cx43: Is It an Effective Approach for the Treatment of Cardiovascular Diseases?Biomolecules · 2025Review
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
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- Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2024Review
- Desmosomal Junctions and Connexin-43 Remodeling in High-Pacing-Induced Heart Failure Dogs.Anatolian journal of cardiology · 2023Article
- Microtubule plus-end tracking proteins: novel modulators of cardiac sodium channels and arrhythmogenesis.Cardiovascular research · 2023Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- Nesprin-1: novel regulator of striated muscle nuclear positioning and mechanotransduction.Biochemical Society transactions · 2023Review
- Hypertension Induces Pro-arrhythmic Cardiac Connexome Disorders: Protective Effects of Treatment.Biomolecules · 2023Review
- Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations.Nature communications · 2022Article
- A microtubule-connexin-43 regulatory link suppresses arrhythmias and cardiac fibrosis in Duchenne muscular dystrophy mice.American journal of physiology. Heart and circulatory physiology · 2022Article
- Review
- Targeting the Microtubule EB1-CLASP2 Complex Modulates NaCirculation research · 2021Article
- Connexins in the Heart: Regulation, Function and Involvement in Cardiac Disease.International journal of molecular sciences · 2021Review
- Importance of Cx43 for Right Ventricular Function.International journal of molecular sciences · 2021Review
- Prevention of connexin-43 remodeling protects against Duchenne muscular dystrophy cardiomyopathy.The Journal of clinical investigation · 2020Article
- β-adrenergic-mediated dynamic augmentation of sarcolemmal CaThe Journal of physiology · 2019Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDesmosomes and adherens junctions provide mechanical continuity between cardiac cells, whereas gap junctions allow for cell-cell electrical/metabolic coupling. These structures reside at the cardiac intercalated disc (ID). Also at the ID is the voltage-gated sodium channel (VGSC) complex. Functional interactions between desmosomes, gap junctions, and VGSC have been demonstrated. Separate studies show, under various conditions, reduced presence of gap junctions at the ID and redistribution of connexin43 (Cx43) to plaques oriented parallel to fiber direction (gap junction "lateralization").
objectiveTo determine the mechanisms of Cx43 lateralization, and the fate of desmosomal and sodium channel molecules in the setting of Cx43 remodeling.
methodsAdult sheep were subjected to right ventricular pressure overload (pulmonary hypertension). Tissue was analyzed by quantitative confocal microscopy and by transmission electron microscopy. Ionic currents were measured using conventional patch clamp.
resultQuantitative confocal microscopy demonstrated lateralization of immunoreactive junctional molecules. Desmosomes and gap junctions in lateral membranes were demonstrable by electron microscopy. Cx43/desmosomal remodeling was accompanied by lateralization of 2 microtubule-associated proteins relevant for Cx43 trafficking: EB1 and kinesin protein Kif5b. In contrast, molecules of the VGSC failed to reorganize in plaques discernable by confocal microscopy. Patch-clamp studies demonstrated change in amplitude and kinetics of sodium current and a small reduction in electrical coupling between cells.
conclusionsCx43 lateralization is part of a complex remodeling that includes mechanical and gap junctions but may exclude components of the VGSC. We speculate that lateralization results from redirectionality of microtubule-mediated forward trafficking. Remodeling of junctional complexes may preserve electrical synchrony under conditions that disrupt ID integrity.
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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 OpenQuestion graph.