Modulation by Topiramate of AMPA and Kainate Mediated Calcium Influx in Cultured Cerebral Cortical, Hippocampal and Cerebellar Neurons

Claus F. Poulsen, Timothy A. Simeone, Thomas E. Maar, Virginia Smith-Swintosky, H. Steven White, Arne Schousboe

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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 μM, 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.

Original languageEnglish (US)
Pages (from-to)275-282
Number of pages8
JournalNeurochemical Research
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2004

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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