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Mature hippocampal astrocytes exhibit functional metabotropic and ionotropic glutamate receptors in situ
Author(s) -
Shelton Marilee K.,
McCarthy Ken D.
Publication year - 1999
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199903)26:1<1::aid-glia1>3.0.co;2-z
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 6 , biology , long term depression , metabotropic glutamate receptor 8 , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 1 , ampa receptor , glutamate receptor , neuroscience , metabotropic receptor , ionotropic effect , metabotropic glutamate receptor 5 , metabotropic glutamate receptor 2 , receptor , biochemistry
Astrocytes closely contact neurons where they respond to neuronally released glutamate in immature brain slices. In previous studies, neither metabotropic nor ionotropic glutamate receptor–mediated responses were detected by imaging Ca 2+ in astrocytes from mature (P21–P42) animals, suggesting astrocyte glutamate receptors only contribute to hippocampus physiology during development. In contrast to Ca 2+ imaging, published electrophysiological experiments suggest P30–P35 astrocytes have α‐amino‐hydroxy‐5‐methyl‐4–isoxazolepropionic acid (AMPA) receptors. For this study, we imaged astrocytes in P31–P38 hippocampal slices to determine if metabotropic and ionotropic glutamate receptor activation elevates intracellular calcium in mature astrocytes. Drugs were perfused while [Ca 2+ ] i was monitored (confocal imaging) in cells loaded with Calcium Green 1‐AM. Imaged cells were subsequently identified as astrocytes by GFAP/S‐100 immunostaining. Astrocytic Ca 2+ increased after glutamate application in the presence of a glutamate uptake inhibitor. An agonist at group I/II metabotropic glutamate receptors, (±)‐1‐aminocyclopentane‐ trans ‐1,3‐dicarboxylic acid (t‐ACPD), elicited Ca 2+ increases as did group I agonist 3,5‐dihydroxyphenylglycine (DHPG), suggesting that mature astrocytes respond to glutamate via metabotropic glutamate receptors. AMPA also elicited Ca 2+ elevations that were inhibited by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and occurred after treatment with ω‐conotoxin MVIIC to block neurotransmitter release. These results demonstrate that astrocytes in mature hippocampus have functional ionotropic and metabotropic glutamate receptors that regulate astrocytic calcium levels. Glutamatergic regulation of astrocytic [Ca 2+ ] i may be involved in synapse modeling, long‐term potentiation, excitotoxicity and other events dependent on glutamatergic transmission in adult hippocampus. GLIA 26:1‐11, 1999. © 1999 Wiley‐Liss, Inc.