ArticleGlia2014
Mechanosensitive release of adenosine 5'-triphosphate through pannexin channels and mechanosensitive upregulation of pannexin channels in optic nerve head astrocytes: a mechanism for purinergic involvement in chronic strain.
Article in Glia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 170 citations in OpenAlex.
- Low-Intensity Focused Ultrasound Neuromodulation in Psychiatric Disorders: Mechanisms, Models, and Missing Links.Biological psychiatry · 2026Review
- Neurovascular coupling and cerebrovascular reactivity: physiology, lifespan development, pathophysiology, and clinical relevance.Frontiers in physiology · 2026Review
- Brief mechanical pulses induce sustained intracellular L-lactate production in astrocytes.Frontiers in cellular neuroscience · 2026Article
- P2X7 receptor-dependent microglia-astrocyte coupling in Alzheimer's disease: from eATP sensing to synaptic and proteostatic failure.Frontiers in aging neuroscience · 2026Review
- Compensatory transporter upregulation facilitates retinal ganglion cell survival in glaucoma after MCT2 elimination.Frontiers in cell and developmental biology · 2026Article
- CXCR3 Deficiency Alleviates Retinal Ganglion Cell Loss by Regulating Neuron-Astrocyte Communication in a Mouse Model of Glaucoma.Investigative ophthalmology & visual science · 2025Article
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- The P2X7 Receptor Regulates IL-1β Secretion in the Human Retina.International journal of molecular sciences · 2025Article
- Rodent Models of Glaucoma: How Mice and Rats Can Help Human Vision Move Out of the Woods and Into the Light.Cells · 2025Review
- Compression injury regulates astrocyte morphology, metabolic function, and extracellular matrix modification in a 3D hydrogel.bioRxiv : the preprint server for biology · 2025Article
- The Multifaceted Role of P2X7R in Microglia and Astrocytes.Neurochemical research · 2025Review
- Extracellular ATP regulates phagocytic activity, mitochondrial respiration, and cytokine secretion of human astrocytic cells.Purinergic signalling · 2025Article
- Priming and release of cytokine IL-1β in microglial cells from the retina.Experimental eye research · 2025Article
- The IL-33/ST2 Axis Protects Retinal Ganglion Cells by Modulating the Astrocyte Response After Optic Nerve Injury.Neuroscience bulletin · 2025Article
- Intraocular Pressure and Retinal Nerve Fiber Layer Changes in a Microgravity Mouse Model and Relevance to Spaceflight-Associated Neuro-Ocular Syndrome.Eye and brain · 2025Article
- Mechanobiology in the eye.npj biological physics and mechanics · 2025Review
- Increased Purinergic Signaling in Human Dental Pulps With Inflammatory Pain is Sex-Dependent.The journal of pain · 2024Article
- The contribution of pattern recognition receptor signalling in the development of age related macular degeneration: the role of toll-like-receptors and the NLRP3-inflammasome.Journal of neuroinflammation · 2024Review
- IOP and glaucoma damage: The essential role of optic nerve head and retinal mechanosensors.Progress in retinal and eye research · 2024Review
- Attenuation of Microglial Activation and Pyroptosis by Inhibition of P2X7 Pathway Promotes Photoreceptor Survival in Experimental Retinal Detachment.Investigative ophthalmology & visual science · 2023Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
As adenosine 5'-triphosphate (ATP) released from astrocytes can modulate many neural signaling systems, the triggers and pathways for this ATP release are important. Here, the ability of mechanical strain to trigger ATP release through pannexin channels and the effects of sustained strain on pannexin expression were examined in rat optic nerve head astrocytes. Astrocytes released ATP when subjected to 5% of equibiaxial strain or to hypotonic swelling. Although astrocytes expressed mRNA for pannexins 1-3, connexin 43, and VNUT, pharmacological analysis suggested a predominant role for pannexins in mechanosensitive ATP release, with Rho kinase contribution. Astrocytes from panx1(-/-) mice had reduced baseline and stimulated levels of extracellular ATP, confirming the role for pannexins. Swelling astrocytes triggered a regulatory volume decrease that was inhibited by apyrase or probenecid. The swelling-induced rise in calcium was inhibited by P2X7 receptor antagonists A438079 and AZ10606120, in addition to apyrase and carbenoxolone. Extended stretch of astrocytes in vitro upregulated expression of panx1 and panx2 mRNA. A similar upregulation was observed in vivo in optic nerve head tissue from the Tg-MYOC(Y437H) mouse model of chronic glaucoma; genes for panx1, panx2, and panx3 were increased, whereas immunohistochemistry confirmed increased expression of pannexin 1 protein. In summary, astrocytes released ATP in response to mechanical strain, with pannexin 1 the predominant efflux pathway. Sustained strain upregulated pannexins in vitro and in vivo. Together, these findings provide a mechanism by which extracellular ATP remains elevated under chronic mechanical strain, as found in the optic nerve head of patients with glaucoma.
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Registered trials
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.