Glutamate receptor agonists stimulate diverse calcium responses in different types of cultured rat cortical glial cells

James A. Holzwarth, Simon J. Gibbons, James R. Brorson, Louis H. Philipson, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


We examined the effects of different types of glutamate receptor agonists on the intracellular calcium concentration, ([Ca2+](i)), in cultured rat cortical glial cells. The cells in these cultures were characterized immunocytochemically using antibodies against glial fibrillary acidic protein, A2B5, and OX-42. The metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid produced Ca2+ mobilization from intracellular stores in all classes of cells. Agonists at non-NMDA glutamate receptors also produced large increases in [Ca2+](i), primarily in cells of the O-2A lineage. Disruption of intracellular Ca2+ stores with thapsigargin showed that increases in [Ca2+](i) produced by activating AMPA/kainate receptors were primarily due to Ca2+ influx rather than Ca2+-induced Ca2+ release. Agonists at NMDA receptors were ineffective. Electrophysiological studies revealed that cells of the O-2A lineage exhibited moderate inward currents in response to kainate in Na+- containing solutions, but only small inward currents and outward rectification in Na+-free solutions. However, in the presence of cyclothiazide, the kainate-induced currents were increased in size and a rightward shift of the reversal potential with increased [Ca2+](o) could be demonstrated. Activation of cells by kainate, but not by depolarizing stimuli, stimulated the uptake of Co2+. Polymerase chain reaction studies showed that the glutamate receptor subunits GluR1-4 and GluR6 were all expressed in these cultures, but GluR5 was absent. The nature of the Ca2+ uptake pathway activated by non-NMDA receptor agonists in the O-2A lineage population is discussed. It is considered most likely that the O-2A lineage cells express both non-NMDA receptors that are relatively impermeable to divalent cations, as well as a smaller population that are Ca2+ permeable.

Original languageEnglish (US)
Pages (from-to)1879-1891
Number of pages13
JournalJournal of Neuroscience
Issue number4
StatePublished - Apr 1994


  • AMPA
  • Ca-permeable glutamate receptor
  • O-2A progenitors
  • astrocytes
  • kainate

ASJC Scopus subject areas

  • General Neuroscience


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