Glutamate-induced intracellular calcium changes and neurotoxicity in cortical neurons in vitro: effect of chemical ischemia.
To study the role of calcium in neuronal death during ischemia, we examined the characteristics of intracellular Ca2+ ([Ca2+]i) changes in single rat forebrain neurons exposed for 5 min to glutamate (3 microM + 1 microM glycine), NMDA (30 microM + 1 microM glycine), kainate (100 microM) or high K+ (50 mM), under both normal and ischemic conditions. The parameters of [Ca2+]i change measured included peak [Ca2+]i level, plateau [Ca2+]i level, area under the [Ca2+]i response curve and time taken by [Ca2+]i to recover to 10% of the peak response. Under normal conditions, all the agonists studied produced similar [Ca2+]i changes. Chemical ischemia simulated by application of 5 mM KCN in glucose-free buffer had no effect on the basal level of [Ca2+]i, but significantly enhanced and prolonged the [Ca2+]i changes produced by all the agonists. However, in toxicity studies, chemical ischemia significantly potentiated the toxicity of only glutamate and N-methyl-D-aspartate. In correlation studies, all the neurons which died displayed an irreversible secondary [Ca2+]i load prior to loss of viability. These studies suggest that while Ca2+ entry may play a critical role in neuronal death, the magnitude of initial [Ca2+]i change does not predict the toxicity of an agonist in cortical neurons.
Rajdev
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Department of Pharmacology, University of Pittsburgh, PA 15261.
Reynolds
I J
IJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000633:toxicity; D018698:Glutamic Acid / Q000494:pharmacology* / Q000633:toxicity; D005998:Glycine / Q000494:pharmacology / Q000633:toxicity; D007608:Kainic Acid / Q000494:pharmacology / Q000633:toxicity; D016202:N-Methylaspartate / Q000494:pharmacology / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D009553:Nimodipine / Q000494:pharmacology / Q000633:toxicity; D011189:Potassium Chloride / Q000494:pharmacology / Q000633:toxicity; D011190:Potassium Cyanide / Q000494:pharmacology / Q000633:toxicity; D016548:Prosencephalon / Q000166:cytology* / Q000196:embryology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018698:Glutamic Acid; D009553:Nimodipine; D016202:N-Methylaspartate; D011189:Potassium Chloride; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D011190:Potassium Cyanide; D007608:Kainic Acid; D002118:Calcium; D005998:Glycine