P2X 7 Receptor-Mediated Release of Excitatory Amino Acids from Astrocytes
Open accessAbstract
Astrocyte glutamate release can modulate synaptic activity and participate in brain intercellular signaling. P2X7 receptors form large ion channels when activated by ATP or other ligands. Here we show that P2X7 receptors provide a route for excitatory amino acid release from astrocytes. Studies were performed using murine cortical astrocyte cultures. ATP produced an inward current in patch-clamped astrocytes with properties characteristic of P2X7 receptor activation: the current was amplified in low divalent cation medium, blocked by pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), and more potently activated by 3'-O-(4-benzoyl)benzoyl ATP (BzATP) than by ATP itself. Measurement of current reversal potentials showed the relative BzATP-induced permeabilities to different substrates to be Na+, 1 > Cl-, 0.34 > N-methyl-D-glucamine, 0.27 > L-glutamate, 0.15 approximately D-aspartate, 0.16. Astrocytes exposed to BzATP also became permeable to Lucifer yellow, indicating a large channel opening. Release of L-glutamate and D-aspartate through P2X7 channels was confirmed using radiolabeled tracers. As with the inward current, release of glutamate and D-aspartate was induced by BzATP more potently than ATP, amplified in Ca2+/Mg2+-free medium, and blocked by PPADS or oxidized ATP. Efflux through P2X7 channels is a previously unrecognized route of ligand-stimulated, nonvesicular astrocyte glutamate release.
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Participation of P2X7R localized in glial cells on the net effect on glutamate release has been indicated by radiolabeled studies in murine cortical astrocyte cultures and whole-cell patch-clamp analysis.
“However, participation of P2X7R localized in glial-cells on the net effect on glutamate release has also been indicated by radiolabeled studies in murine cortical astrocyte cultures [110] and whole-cell patch-clamp analysis [111].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [110]
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“These changes are consistent with previous results showing that the activation of P2rx7s in the brain leads to an increased glutamate and GABA release from nerve terminals (Papp et al. 2004; Patti et al. 2006; Sperlagh et al. 2002) and astrocytes (Duan et al. 2003).”
ResultLack of ATP-evoked GABA and glutamate release in the hippocampus of P2X7 receptor-/- mice
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- Authors
- Duan, S., Anderson, C. M., Keung, E. C., Chen, Y., Chen, Y., & Swanson, R. A.
- Affiliations
- Pediatrics and Genetics (US)
- San Francisco VA Medical Center (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-02-15
- Volume
- 23
- Issue
- 4
- Pages
- 1320-1328
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6742264
- OpenAlex
- W1516426911
- Cited by
- 489
- References
- 68
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 8 · 2023: 11 · 2022: 13 · 2021: 18 · 2020: 14 · 2019: 23 · 2018: 14 · 2017: 14 · 2016: 26 · 2015: 21 · 2014: 14 · 2013: 24 · 2012: 23
- FWCI
- 17.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Heart and Stroke Foundation of Canada
- National Institutes of Health
- Canadian Institutes of Health Research
- National Cancer Institute (R01CA094121)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- P2X7 receptor, astrocytes, glutamate release, D-aspartate release, excitatory amino acids, ATP, BzATP, PPADS, ion channel permeability, divalent cation dependence, cortical astrocytes
- MeSH terms
- Adenosine Triphosphate, Animals, Astrocytes, Biological Transport, Brain, Cells, Cultured, Electric Conductivity, Isoquinolines, Receptors, Purinergic P2, Patch-Clamp Techniques, Glutamic Acid, Excitatory Amino Acids, Mice, Receptors, Purinergic P2X7
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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