ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2011
Connexin channels provide a target to manipulate brain endothelial calcium dynamics and blood-brain barrier permeability.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.Nature genetics · 2016Pooled it
- Cellular Characterization Using Microwave-Assisted Immunocytochemistry, A Time-Efficient Alternative to Traditional Immunocytochemistry.Current protocols · 2026Article
- Heterogeneity of astrocyte density, morphology and connexins in the mouse hippocampus.Frontiers in neuroanatomy · 2026Article
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Dynamic modulation of the blood-brain barrier in the healthy brain.Nature reviews. Neuroscience · 2025Review
- Calcium Regulation of Connexin Hemichannels.International journal of molecular sciences · 2024Review
- Astroglial connexin 43 is a novel therapeutic target for chronic multiple sclerosis model.Scientific reports · 2024Article
- Control of astrocytic CaBiological research · 2024Article
- Long-term impact of maternal obesity on the gliovascular unit and ephrin signaling in the hippocampus of adult offspring.Journal of neuroinflammation · 2024Article
- Cracking the Endothelial Calcium (CaInternational journal of molecular sciences · 2023Review
- MLKL regulates Cx43 ubiquitinational degradation and mediates neuronal necroptosis in ipsilateral thalamus after focal cortical infarction.Molecular brain · 2023Article
- Opening of Cx43-formed hemichannels mediates the CaBiology direct · 2023Article
- Somatic GJA4 gain-of-function mutation in orbital cavernous venous malformations.Angiogenesis · 2023Article
- The Involvement of Cx43 in JNK1/2-Mediated Endothelial Mechanotransduction and Human Plaque Progression.International journal of molecular sciences · 2023Article
- Targeting gliovascular connexins prevents inflammatory blood-brain barrier leakage and astrogliosis.JCI insight · 2022Article
- Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.International journal of molecular sciences · 2022Review
- Connexins, Pannexins and Gap Junctions in Perinatal Brain Injury.Biomedicines · 2022Review
- Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth.International journal of molecular sciences · 2022Article
- Synthesis and Biological Evaluation of Termini-Modified and Cyclic Variants of the Connexin43 Inhibitor Peptide5.Frontiers in chemistry · 2022Article
- Review
15 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 7 institutions in 4 countries.
Funding
Abstract
The cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) is an important factor determining the functional state of blood-brain barrier (BBB) endothelial cells but little is known on the effect of dynamic [Ca(2+)](i) changes on BBB function. We applied different agonists that trigger [Ca(2+)](i) oscillations and determined the involvement of connexin channels and subsequent effects on endothelial permeability in immortalized and primary brain endothelial cells. The inflammatory peptide bradykinin (BK) triggered [Ca(2+)](i) oscillations and increased endothelial permeability. The latter was prevented by buffering [Ca(2+)](i) with BAPTA, indicating that [Ca(2+)](i) oscillations are crucial in the permeability changes. Bradykinin-triggered [Ca(2+)](i) oscillations were inhibited by interfering with connexin channels, making use of carbenoxolone, Gap27, a peptide blocker of connexin channels, and Cx37/43 knockdown. Gap27 inhibition of the oscillations was rapid (within minutes) and work with connexin hemichannel-permeable dyes indicated hemichannel opening and purinergic signaling in response to stimulation with BK. Moreover, Gap27 inhibited the BK-triggered endothelial permeability increase in in vitro and in vivo experiments. By contrast, [Ca(2+)](i) oscillations provoked by exposure to adenosine 5' triphosphate (ATP) were not affected by carbenoxolone or Gap27 and ATP did not disturb endothelial permeability. We conclude that interfering with endothelial connexin hemichannels is a novel approach to limiting BBB-permeability alterations.
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