ArticleThe Journal of biological chemistry2012
Connexin 43 hemichannels contribute to cytoplasmic Ca2+ oscillations by providing a bimodal Ca2+-dependent Ca2+ entry pathway.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 116 citations in OpenAlex.
- Voltage-Dependent Ion Channels in Vascular Endothelial Cells: An Unexpected Signaling Pathway in Non-Excitable Cells.Biomedicines · 2026Review
- Tanycyte-derived lactate activates astrocytic HCAR1 to modulate glutamatergic signaling and POMC neuron excitability.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Astrocytic Connexin43 Channels Are Essential for Breathing Pattern Stabilization in the preBötzinger Complex.CNS neuroscience & therapeutics · 2025Article
- Endothelial TRPV4-Cx43 signalling complex regulates vasomotor tone in resistance arteries.The Journal of physiology · 2025Article
- The innexin 7 gap junction protein contributes to synchronized activity in theFrontiers in neural circuits · 2025Article
- Connexin-43 in Cancer: Above and Beyond Gap Junctions!Cancers · 2024Review
- Connexins and Aging-Associated Respiratory Disorders: The Role in Intercellular Communications.Biomedicines · 2024Review
- Endothelial TRPV4/Cx43 Signaling Complex Regulates Vasomotor Tone in Resistance Arteries.bioRxiv : the preprint server for biology · 2024Article
- Inhibition of astroglial hemichannels prevents synaptic transmission decline during spreading depression.Biological research · 2024Article
- Hemichannels contribute to mitochondrial CaFrontiers in cell and developmental biology · 2024Article
- Acute activation of hemichannels by ethanol leads to CaFrontiers in cell and developmental biology · 2024Article
- SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular CaBiological research · 2023Article
- Opening of Cx43-formed hemichannels mediates the CaBiology direct · 2023Article
- Connexin 37 sequestering of activated-ERK in the cytoplasm promotes p27-mediated endothelial cell cycle arrest.Life science alliance · 2023Article
- 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
- The Polyamine Spermine Potentiates the Propagation of Negatively Charged Molecules through the Astrocytic Syncytium.Biomolecules · 2022Article
- Mechanosensitive piezo1 calcium channel activates connexin 43 hemichannels through PI3K signaling pathway in bone.Cell & bioscience · 2022Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many cellular functions are driven by changes in the intracellular Ca(2+) concentration ([Ca(2+)](i)) that are highly organized in time and space. Ca(2+) oscillations are particularly important in this respect and are based on positive and negative [Ca(2+)](i) feedback on inositol 1,4,5-trisphosphate receptors (InsP(3)Rs). Connexin hemichannels are Ca(2+)-permeable plasma membrane channels that are also controlled by [Ca(2+)](i). We aimed to investigate how hemichannels may contribute to Ca(2+) oscillations. Madin-Darby canine kidney cells expressing connexin-32 (Cx32) and Cx43 were exposed to bradykinin (BK) or ATP to induce Ca(2+) oscillations. BK-induced oscillations were rapidly (minutes) and reversibly inhibited by the connexin-mimetic peptides (32)Gap27/(43)Gap26, whereas ATP-induced oscillations were unaffected. Furthermore, these peptides inhibited the BK-triggered release of calcein, a hemichannel-permeable dye. BK-induced oscillations, but not those induced by ATP, were dependent on extracellular Ca(2+). Alleviating the negative feedback of [Ca(2+)](i) on InsP(3)Rs using cytochrome c inhibited BK- and ATP-induced oscillations. Cx32 and Cx43 hemichannels are activated by <500 nm [Ca(2+)](i) but inhibited by higher concentrations and CT9 peptide (last 9 amino acids of the Cx43 C terminus) removes this high [Ca(2+)](i) inhibition. Unlike interfering with the bell-shaped dependence of InsP(3)Rs to [Ca(2+)](i), CT9 peptide prevented BK-induced oscillations but not those triggered by ATP. Collectively, these data indicate that connexin hemichannels contribute to BK-induced oscillations by allowing Ca(2+) entry during the rising phase of the Ca(2+) spikes and by providing an OFF mechanism during the falling phase of the spikes. Hemichannels were not sufficient to ignite oscillations by themselves; however, their contribution was crucial as hemichannel inhibition stopped the oscillations.
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