Mature hippocampal astrocytes exhibit functional metabotropic and ionotropic glutamate receptors in situ

✍ Scribed by Marilee K. Shelton; Ken D. McCarthy

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 323 KB
• Volume: 26
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/(sici)1098-1136(199903)26:1<1::aid-glia1>3.0.co;2-z

✦ Synopsis

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 2ϩ in astrocytes from mature (P21-P42) animals, suggesting astrocyte glutamate receptors only contribute to hippocampus physiology during development. In contrast to Ca 2ϩ imaging, published electrophysiological experiments suggest P30-P35 astrocytes have ␣-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 2ϩ ] 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 2ϩ increased after glutamate application in the presence of a glutamate uptake inhibitor. An agonist at group I/II metabotropic glutamate receptors, (Ϯ)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD), elicited Ca 2ϩ 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 2ϩ elevations that were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and occurred after treatment with -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 2ϩ ] i may be involved in synapse modeling, long-term potentiation, excitotoxicity and other events dependent on glutamatergic transmission in adult hippocampus.