ArticleBasic research in cardiology2012
Connexin mimetic peptides inhibit Cx43 hemichannel opening triggered by voltage and intracellular Ca2+ elevation.
Article in Basic research in cardiology, 2012. 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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Who cites it
87 citing papers in PubMed, 153 citations in OpenAlex.
- Interferon-γ Mitigates Oxaliplatin-Induced Neurotoxicity: Analogies With Connexin 43.CNS neuroscience & therapeutics · 2026Article
- Connexin 50 mediates disease-relevant alpha-synuclein oligomer propagation and neuroinflammation in neurodegenerative disease.iScience · 2026Article
- Simultaneous Whole-Cell Recording and Calcium Imaging Does Not Reveal Electrically Coupled Neurons ineNeuro · 2026Article
- Article
- Endothelial TRPV4-Cx43 signalling complex regulates vasomotor tone in resistance arteries.The Journal of physiology · 2025Article
- Connexin43 hemichannel blockade turns microglia neuroprotective and mitigates cognitive deficits in a mouse model of amyloidosis.Nature communications · 2025Article
- Overexpression of Cx43: Is It an Effective Approach for the Treatment of Cardiovascular Diseases?Biomolecules · 2025Review
- Connexin 43 hemichannels and related diseases.Antibody therapeutics · 2024Review
- Endothelial TRPV4/Cx43 Signaling Complex Regulates Vasomotor Tone in Resistance Arteries.bioRxiv : the preprint server for biology · 2024Article
- Calcium Regulation of Connexin Hemichannels.International journal of molecular sciences · 2024Review
- Extracellular vesicles released by LPS-stimulated spinal organotypic slices spread neuroinflammation into naïve slices through connexin43 hemichannel opening and astrocyte aberrant calcium dynamics.Frontiers in cellular neuroscience · 2024Article
- Vascular Endothelial Barrier Protection Prevents Atrial Fibrillation by Preserving Cardiac Nanostructure.JACC. Clinical electrophysiology · 2023Article
- Cx43 Hemichannel and Panx1 Channel Modulation by Gap19 andInternational journal of molecular sciences · 2023Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- Mitochondrial Connexins and Mitochondrial Contact Sites with Gap Junction Structure.International journal of molecular sciences · 2023Review
- Connexin hemichannels as candidate targets for cardioprotective and anti-arrhythmic treatments.The Journal of clinical investigation · 2023Review
- Gap Junctions and Connexins in Microglia-Related Oxidative Stress and Neuroinflammation: Perspectives for Drug Discovery.Biomolecules · 2023Review
- The roles of connexins and gap junctions in the progression of cancer.Cell communication and signaling : CCS · 2023Review
- Inhibition of connexin hemichannels alleviates neuroinflammation and hyperexcitability in temporal lobe epilepsy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Targeting gliovascular connexins prevents inflammatory blood-brain barrier leakage and astrogliosis.JCI insight · 2022Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
Abstract
Connexin mimetic peptides (CxMPs), such as Gap26 and Gap27, are known as inhibitors of gap junction channels but evidence is accruing that these peptides also inhibit unapposed/non-junctional hemichannels (HCs) residing in the plasma membrane. We used voltage clamp studies to investigate the effect of Gap26/27 at the single channel level. Such an approach allows unequivocal identification of HC currents by their single channel conductance that is typically ~220 pS for Cx43. In HeLa cells stably transfected with Cx43 (HeLa-Cx43), Gap26/27 peptides inhibited Cx43 HC unitary currents over minutes and increased the voltage threshold for HC opening. By contrast, an elevation of intracellular calcium ([Ca(2+)](i)) to 200-500 nM potentiated the unitary HC current activity and lowered the voltage threshold for HC opening. Interestingly, Gap26/27 inhibited the Ca(2+)-potentiated HC currents and prevented lowering of the voltage threshold for HC opening. Experiments on isolated pig ventricular cardiomyocytes, which display strong endogenous Cx43 expression, demonstrated voltage-activated unitary currents with biophysical properties of Cx43 HCs that were inhibited by small interfering RNA targeting Cx43. As observed in HeLa-Cx43 cells, HC current activity in ventricular cardiomyocytes was potentiated by [Ca(2+)](i) elevation to 500 nM and was inhibited by Gap26/27. Our results indicate that under pathological conditions, when [Ca(2+)](i) is elevated, Cx43 HC opening is promoted in cardiomyocytes and CxMPs counteract this effect.
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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.