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PMID: 12598620 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

P2X7 receptor-mediated release of excitatory amino acids from astrocytes.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 23 ·No. 4 ·2003-02-15 ·Pages 1320-8

Duan S, Anderson CM, Keung EC, Chen Y, Chen Y, Swanson RA

Abstract

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.

MeSH Terms
Adenosine Triphosphate/analogs & derivatives,pharmacology Animals Astrocytes/drug effects,metabolism,physiology Biological Transport Brain/cytology,physiology Cells, Cultured Electric Conductivity Excitatory Amino Acids/metabolism Glutamic Acid/metabolism Isoquinolines/metabolism Mice Patch-Clamp Techniques Receptors, Purinergic P2/physiology Receptors, Purinergic P2X7
Chemicals
Excitatory Amino Acids Isoquinolines P2rx7 protein, mouse Receptors, Purinergic P2 Receptors, Purinergic P2X7 Glutamic Acid 3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate Adenosine Triphosphate lucifer yellow
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Duan Shumin
Department of Neurology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, California 94121, USA.
Anderson Christopher M
Keung Edmund C
Chen Yongmei
Chen Yiren
Swanson Raymond A
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2003-02-15
Pages
1320-8
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6742264
Subset
IM
Grants
NCI NIH HHS · R01 CA094121 · United States
External Links
PubMed source PMC Full Text View journal details
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