Glutamate receptors activate Ca2+ mobilization and Ca2+ influx into astrocytes

Steven R. Glaum, James A. Holzwarth, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

198 Scopus citations

Abstract

We measured changes in the molar concentration of cytosolic Ca2+ ([Ca2+]i) in individual astrocytes in culture produced by the glutamate analog quisqualate (QA) and related substances by using fura-2 digital fluorescence microscopy. In cells cultured from the cortex, hippocampus, and cerebellum, the QA analog a-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA; 10 μM) produced a slow increase in [Ca2+]i that was modest in amplitude (≈200 nM). These effects were completely abolished by 10 μM 6-nitro-7-cyano-quinoxaline-2,3-dione (CNQX). In cerebellar astrocytes, similar effects were produced by QA. However, in cortical and hippocampal astrocytes, the response to QA was much more complex. In these cells, QA produced an initial [Ca2+]i spike that was followed by a sustained influx of Ca2+ ("plateau"). In the absence of extracellular Ca2+, this plateau was abolished but the spike remained. CNQX did not block the spike and only slightly reduced the size of the plateau in some cells. Ni2+ (10 μM) but not nimodipine (10 μM) reduced the amplitude of the plateau. Pretreatment with 100 nM phorbol 12-myristate 13-acetate for 15 min abolished the spike but not the plateau portion of the QA response. Treatment with pertussis toxin at 250 ng/ml for 12-16 hr failed to alter the response. In some instances, the latency of the QA response differed considerably for individual cells in a group. It appeared that the response began in one cell and then spread to neighboring cells. Thus, QA appears to trigger a complex response in some astrocytes consisting of Ca2+ mobilization from intracellular stores and also Ca2+ influx resulting from the activation of AMPA-sensitive and -insensitive pathways.

Original languageEnglish (US)
Pages (from-to)3454-3458
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number9
DOIs
StatePublished - May 1990

Keywords

  • Inositol trisphosphate
  • Quisqualate

ASJC Scopus subject areas

  • General

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