ArticleCardiovascular research2014
Super-resolution imaging reveals that loss of the C-terminus of connexin43 limits microtubule plus-end capture and NaV1.5 localization at the intercalated disc.
Article in Cardiovascular research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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87 citing papers in PubMed, 130 citations in OpenAlex.
- Decreasing Microtubule Detyrosination Improves Cardiac Mechanics and Sodium Channel Function in Arrhythmogenic Cardiomyopathy.Circulation. Arrhythmia and electrophysiology · 2026Article
- Connexin43 Deficiency Leads to Ventricular Arrhythmias by Reprogramming Proline Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The influence of intercalated disk nanostructure on local ionic currents and cardiac conduction.Biophysical journal · 2026Article
- Transcriptomic and proteomic profiling shows dysregulated immune and metabolic pathways in arrhythmogenic cardiomyopathy.ESC heart failure · 2025Article
- Correlative imaging integrates electrophysiology with three-dimensional murine heart reconstruction to reveal electrical coupling between cell types.Nature cardiovascular research · 2025Article
- Epigenetic regulation of electromechanical continuity might determine phenotypic heterogeneity in SCN5A mutation carriers in Brugada syndrome.Scientific reports · 2025Article
- Exercise-induced dysregulation of the adrenergic response in a mouse model of PKP2-arrhythmogenic cardiomyopathy.Heart rhythm · 2025Article
- SCN10A-short gene therapy to restore conduction and protect against malignant cardiac arrhythmias.European heart journal · 2025Article
- 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
- Cardiomyocyte Reduction of Hybrid/Complex N-Glycosylation in the Adult Causes Heart Failure With Reduced Ejection Fraction in the Absence of Cellular Remodeling.Journal of the American Heart Association · 2024Article
- Connexin43 promotes exocytosis of damaged lysosomes through actin remodelling.The EMBO journal · 2024Article
- Decreasing microtubule detyrosination modulates Nav1.5 subcellular distribution and restores sodium current in mdx cardiomyocytes.Cardiovascular research · 2024Article
- Indirect Correlative Light and Electron Microscopy (iCLEM): A Novel Pipeline for Multiscale Quantification of Structure From Molecules to Organs.Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada · 2024Article
- Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis.Circulation research · 2024Article
- Unraveling Impacts of Chamber-Specific Differences in Intercalated Disc Ultrastructure and Molecular Organization on Cardiac Conduction.JACC. Clinical electrophysiology · 2023Article
- Sodium channel subpopulations with distinct biophysical properties and subcellular localization enhance cardiac conduction.The Journal of general physiology · 2023Article
- 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
27 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsIt is well known that connexin43 (Cx43) forms gap junctions. We recently showed that Cx43 is also part of a protein-interacting network that regulates excitability. Cardiac-specific truncation of Cx43 C-terminus (mutant 'Cx43D378stop') led to lethal arrhythmias. Cx43D378stop localized to the intercalated disc (ID); cell-cell coupling was normal, but there was significant sodium current (INa) loss. We proposed that the microtubule plus-end is at the crux of the Cx43-INa relation. Yet, specific localization of relevant molecular players was prevented due to the resolution limit of fluorescence microscopy. Here, we use nanoscale imaging to establish: (i) the morphology of clusters formed by the microtubule plus-end tracking protein 'end-binding 1' (EB1), (ii) their position, and that of sodium channel alpha-subunit NaV1.5, relative to N-cadherin-rich sites, and (iii) the role of Cx43 C-terminus on the above-mentioned parameters and on the location-specific function of INa. METHODS AND
resultsSuper-resolution fluorescence localization microscopy in murine adult cardiomyocytes revealed EB1 and NaV1.5 as distinct clusters preferentially localized to N-cadherin-rich sites. Extent of co-localization decreased in Cx43D378stop cells. Macropatch and scanning patch clamp showed reduced INa exclusively at cell end, without changes in unitary conductance. Experiments in Cx43-modified HL1 cells confirmed the relation between Cx43, INa, and microtubules.
conclusionsNaV1.5 and EB1 localization at the cell end is Cx43-dependent. Cx43 is part of a molecular complex that determines capture of the microtubule plus-end at the ID, facilitating cargo delivery. These observations link excitability and electrical coupling through a common molecular mechanism.
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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.