Excitatory amino acid‐induced alterations of cytoplasmic free Ca2+ individual cerebellar granule neurons: Role in neurotoxicity
- 1 March 1991
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 28 (3), 434-441
- https://doi.org/10.1002/jnr.490280317
Abstract
The effects of glutamate on intracellular free Ca2+ [Ca2+]i, and neurotoxicity were compared in cerebellar granule neurons in vitro. [Ca2+]i, was measured with fura‐2 and digital fluorescence imaging microscopy; neurotoxicity was monitored using a vital dye and colorimetric analysis. Glutamate produced dosedependent increases in [Ca2+]XSi transient for glutamate concentrations in a range of : 0.01–0.5 μM and sustained for higher levels of glutamate. The ED50 for the [Ca2+]i response to glutamate was. 6 μM. The LQ50 for glutamate‐induced neurotoxicity was similar, i.e., 10 μM The effect of glutamate on [Ca2+]i was greatly dmiinished when external Ca2+ was removed and blocked by Mg2++ N‐methyl‐D‐aspartate (NMDA)‐type receptor antagonists. The latter conditions as well as preloading granule neurons with the intracellular Ca2+ chelator quin2 largely prevented glutamate cytotoxicity. The neurotoxic effect of glutamate required incubations with the stimulus for 10–20 min at 25°C. Withdrawal of glutamate after this period was accompanied by a prolonged alteration in [Ca2+]i. Pretreatment cells with the ganglioside GM1 reduced this late increase in [Ca2+]i, as well as the neurotoxic effects of glutamate. This indicates that glutamate‐induced neurotoxicity results from a composite of diverse temporal alterations in Ca2+ homeostasis and that blunting any of these components reduces excitotoxicity.Keywords
This publication has 48 references indexed in Scilit:
- Glutamate receptor activation in cultured cerebellar granule cells increases cytosolic free Ca2+ by mobilization of cellular Ca2+ and activation of Ca2+ influxExperimental Brain Research, 1989
- Gangliosides prevent glutamate and kainate neurotoxicity in primary neuronal cultures of neonatal rat cerebellum and cortex.Proceedings of the National Academy of Sciences, 1988
- Sustained Dendritic Gradients of Ca 2+ Induced by Excitatory Amino Acids in CA1 Hippocampal NeuronsScience, 1988
- Stimulation of the receptor has a trophic effect on differentiating cerebellar granule cellsNeuroscience Letters, 1988
- Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damageTrends in Neurosciences, 1988
- NMDA receptors - their role in long-term potentiationTrends in Neurosciences, 1987
- Electrophysiological studies of NMDA receptorsTrends in Neurosciences, 1987
- Multiple-conductance channels activated by excitatory amino acids in cerebellar neuronsNature, 1987
- Calcium and Ischemic InjuryNew England Journal of Medicine, 1986
- Pharmacologically distinct glutamate receptors on cerebellar granule cellsLife Sciences, 1986