Modulation by Topiramate of AMPA and Kainate Mediated Calcium Influx in Cultured Cerebral Cortical,Hippocampal and Cerebellar Neurons |
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Authors: | Poulsen Claus F Simeone Timothy A Maar Thomas E Smith-Swintosky Virginia White H Steven Schousboe Arne |
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Institution: | Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark. |
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Abstract: | The effect of the antiepileptic drug topiramate on Ca2+ uptake through (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate (AMPA) and kainate (KA) receptors was investigated in different cell culture systems consisting of neurons from the cerebral cortex, hippocampus, and cerebellum. Ca2+ influx was assayed using a fluorescent Ca2+ chelator to monitor changes in the intracellular Ca2+ concentration or cobalt staining to assess the effect of topiramate on Ca2+-permeable AMPA/KA receptors. In all types of neuronal cultures studied, AMPA and KA were found to elicit an influx of Ca2+ in a subset of the neuronal population. Topiramate, at concentrations of 30 and 100 microM, inhibited Ca2+ influx by up to 60%. Modulation of AMPA and KA-evoked Ca2+ influx may contribute to both the antiepileptic and neuroprotective properties of topiramate. |
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Keywords: | Desensitization receptors glutamate N-methyl-D-aspartate NMDA |
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