ArticleInternational journal of molecular sciences2018
Cx43 Channel Gating and Permeation: Multiple Phosphorylation-Dependent Roles of the Carboxyl Terminus.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Inhibition of Pyk2 prevents Cx43 remodeling and cardiomyocyte injury during hypoxic and adrenergic stress.Journal of molecular and cellular cardiology · 2026Article
- Boldine treatment prevents chronic cognitive impairment and exaggerated fear learning in rats exposed to repetitive low-level blast injury.Frontiers in cellular neuroscience · 2026Article
- The Cx43-Mediated Autophagy Mechanism Influences Triple-Negative Breast Cancer Through the Regulation of Rab31.Cancers · 2025Article
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- Research progress of connexin 43 in cardiovascular diseases.Frontiers in cardiovascular medicine · 2025Review
- Role of astrocytes connexins - pannexins in acute brain injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights.Vascular health and risk management · 2024Review
- Modeling and analysis of voltage gating of gap junction channels at a single-channel level.Biophysical journal · 2023Article
- Channel Behavior and Voltage Gating of a Cx43 Mutant Simulating Preconditioning.Bioelectricity · 2023Article
- Connexin 43 Phosphorylation: Implications in Multiple Diseases.Molecules (Basel, Switzerland) · 2023Review
- Novel Antidepressant Mechanism of Ginsenoside Rg1 in Regulating the Dysfunction of the Glutamatergic System in Astrocytes.International journal of molecular sciences · 2022Article
- Connexin43 in Musculoskeletal System: New Targets for Development and Disease Progression.Aging and disease · 2022Article
- Review
- Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine.Journal of cardiovascular development and disease · 2021Review
- Connexin 43 phosphorylation by casein kinase 1 is essential for the cardioprotection by ischemic preconditioning.Basic research in cardiology · 2021Article
- Novel Tocolytic Strategy: Modulating Cx43 Activity byThe Journal of pharmacology and experimental therapeutics · 2021Article
- Astroglial Connexins in Neurodegenerative Diseases.Frontiers in molecular neuroscience · 2021Review
- Abnormal Expression of Connexin43 in Cardiac Injury Induced by S-Band and X-Band Microwave Exposure in Rats.Journal of immunology research · 2021Article
- Prevention of connexin-43 remodeling protects against Duchenne muscular dystrophy cardiomyopathy.The Journal of clinical investigation · 2020Article
- The Multifaceted Role of Astrocyte Connexin 43 in Ischemic Stroke Through Forming Hemichannels and Gap Junctions.Frontiers in neurology · 2020Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Connexin 43 (Cx43), a gap junction protein seemingly fit to support cardiac impulse propagation and synchronic contraction, is phosphorylated in normoxia by casein kinase 1 (CK1). However, during cardiac ischemia or pressure overload hypertrophy, this phosphorylation fades, Cx43 abundance decreases at intercalated disks and increases at myocytes' lateral borders, and the risk of arrhythmia rises. Studies in wild-type and transgenic mice indicate that enhanced CK1-phosphorylation of Cx43 protects from arrhythmia, while dephosphorylation precedes arrhythmia vulnerability. The mechanistic bases of these Cx43 (de)phosphoform-linked cardiac phenotypes are unknown. We used patch-clamp and dye injection techniques to study the channel function (gating, permeability) of Cx43 mutants wherein CK1-targeted serines were replaced by aspartate (Cx43-CK1-D) or alanine (Cx43-CK1-A) to emulate phosphorylation and dephosphorylation, respectively. Cx43-CK1-D, but not Cx43-CK1-A, displayed high Voltage-sensitivity and variable permselectivity. Both mutants showed multiple channel open states with overall increased conductivity, resistance to acidification-induced junctional uncoupling, and hemichannel openings in normal external calcium. Modest differences in the mutant channels' function and regulation imply the involvement of dissimilar structural conformations of the interacting domains of Cx43 in electrical and chemical gating that may contribute to the divergent phenotypes of CK1-(de)phospho-mimicking Cx43 transgenic mice and that may bear significance in arrhythmogenesis.
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