ArticleBasic research in cardiology2013
Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injury.
Article in Basic research in cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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Who cites it
155 citing papers in PubMed, 251 citations in OpenAlex.
- A Multicenter Randomized Controlled Trial Evaluating a Cx43-Mimetic Peptide in Cutaneous Scarring.The Journal of investigative dermatology · 2017Trial
- Reduced Cx43 S-nitrosylation protects against cardiac stress-induced arrhythmias and myocardial injury in Duchenne muscular dystrophy.Cardiovascular research · 2026Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Connexin 43 in Pathophysiology of Cardiac Diseases: From Molecular Mechanisms to Therapeutic Strategies.Physiological research · 2025Review
- Astrocytic Connexin43 Channels Are Essential for Breathing Pattern Stabilization in the preBötzinger Complex.CNS neuroscience & therapeutics · 2025Article
- Connexin43 and Its Regulation of Astrocyte Gap Junction Function: Influencing Depression Progression by Mediating Electrical and Chemical Signals.CNS neuroscience & therapeutics · 2025Review
- Involvement of connexin 43 in myocardial ischemia-reperfusion injury.Cell and tissue research · 2025Review
- Endothelial TRPV4-Cx43 signalling complex regulates vasomotor tone in resistance arteries.The Journal of physiology · 2025Article
- Targeting Connexin 43 in Retinal Astrocytes Promotes Neuronal Survival in Glaucomatous Injury.Glia · 2025Article
- Megakaryocytes transfer mitochondria to bone marrow mesenchymal stromal cells to lower platelet activation.The Journal of clinical investigation · 2025Article
- Overexpression of Cx43: Is It an Effective Approach for the Treatment of Cardiovascular Diseases?Biomolecules · 2025Review
- Optogenetic quantification of cardiac excitability and electrical coupling in intact hearts to explain cardiac arrhythmia initiation.Science advances · 2025Article
- The role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Astrocytic connexin 43-hemichannels aggravate seizures by modulating blood-brain barrier permeability in temporal lobe epilepsy mice.Pediatric discovery · 2024Article
- Connexin 43 modulates reverse electron transfer in cardiac mitochondria from inducible knock-out Cx43Basic research in cardiology · 2024Article
- Calcium Regulation of Connexin Hemichannels.International journal of molecular sciences · 2024Review
- Photocatalytic manipulation of CaScience advances · 2024Article
- Article
- In vivo therapy of osteosarcoma using anion transporters-based supramolecular drugs.Journal of nanobiotechnology · 2024Article
- Connexins in epidermal health and diseases: insights into their mutations, implications, and therapeutic solutions.Frontiers in physiology · 2024Review
95 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 10 institutions in 5 countries.
Funding
Abstract
Connexin-43 (Cx43), a predominant cardiac connexin, forms gap junctions (GJs) that facilitate electrical cell-cell coupling and unapposed/nonjunctional hemichannels that provide a pathway for the exchange of ions and metabolites between cytoplasm and extracellular milieu. Uncontrolled opening of hemichannels in the plasma membrane may be deleterious for the myocardium and blocking hemichannels may confer cardioprotection by preventing ionic imbalance, cell swelling and loss of critical metabolites. Currently, all known hemichannel inhibitors also block GJ channels, thereby disturbing electrical cell-cell communication. Here we aimed to characterize a nonapeptide, called Gap19, derived from the cytoplasmic loop (CL) of Cx43 as a hemichannel blocker and examined its effect on hemichannel currents in cardiomyocytes and its influence in cardiac outcome after ischemia/reperfusion. We report that Gap 19 inhibits Cx43 hemichannels without blocking GJ channels or Cx40/pannexin-1 hemichannels. Hemichannel inhibition is due to the binding of Gap19 to the C-terminus (CT) thereby preventing intramolecular CT-CL interactions. The peptide inhibited Cx43 hemichannel unitary currents in both HeLa cells exogenously expressing Cx43 and acutely isolated pig ventricular cardiomyocytes. Treatment with Gap19 prevented metabolic inhibition-enhanced hemichannel openings, protected cardiomyocytes against volume overload and cell death following ischemia/reperfusion in vitro and modestly decreased the infarct size after myocardial ischemia/reperfusion in mice in vivo. We conclude that preventing Cx43 hemichannel opening with Gap19 confers limited protective effects against myocardial ischemia/reperfusion injury.
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