title: Glutamate receptor agonists stimulate diverse calcium responses in different types of cultured rat cortical glial cells.
abstract: 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 Ca(2+)-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.
authors.affiliation: Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
authors.forename: J A
authors.initials: JA
authors.lastname: Holzwarth
authors.forename: S J
authors.initials: SJ
authors.lastname: Gibbons
authors.forename: J R
authors.initials: JR
authors.lastname: Brorson
authors.forename: L H
authors.initials: LH
authors.lastname: Philipson
authors.forename: R J
authors.initials: RJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017931:DNA Primers; D016257:Fura-2; D005727:Ganglia, Spinal / Q000378:metabolism / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017470:Receptors, Glutamate / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
chemical_list: D017931:DNA Primers; D005904:Glial Fibrillary Acidic Protein; D046911:Macromolecular Substances; D009498:Neurotoxins; D017470:Receptors, Glutamate; D013729:Terpenes; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D007608:Kainic Acid; D002118:Calcium; D016257:Fura-2