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

doi:10.1023/B:NERE.0000010456.92887.3b

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

Department of Pharmacology and Neuroscience

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

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 language	English (US)
Pages (from-to)	275-282
Number of pages	8
Journal	Neurochemical Research
Volume	29
Issue number	1
DOIs	https://doi.org/10.1023/B:NERE.0000010456.92887.3b
State	Published - Jan 2004

All Science Journal Classification (ASJC) codes

Biochemistry
Cellular and Molecular Neuroscience

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

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.",

author = "Poulsen, {Claus F.} and Simeone, {Timothy A.} and Maar, {Thomas E.} and Virginia Smith-Swintosky and White, {H. Steven} and Arne Schousboe",

note = "Funding Information: The secretarial assistance of Ms. Hanne Dan{\o} and the technical assistance of Ms. Lone Rosenquist and Ms. Kirsten Thuesen is greatly appreciated. The work has been supported by Johnson & Johnson Pharmaceutical Research and Development.",

year = "2004",

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doi = "10.1023/B:NERE.0000010456.92887.3b",

language = "English (US)",

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AU - Simeone, Timothy A.

AU - Maar, Thomas E.

AU - Smith-Swintosky, Virginia

AU - White, H. Steven

AU - Schousboe, Arne

N1 - Funding Information: The secretarial assistance of Ms. Hanne Danø and the technical assistance of Ms. Lone Rosenquist and Ms. Kirsten Thuesen is greatly appreciated. The work has been supported by Johnson & Johnson Pharmaceutical Research and Development.

PY - 2004/1

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N2 - 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.

AB - 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.

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

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