Modulation by topiramate of AMPA and kainate mediated calcium influx in cultured cerebral cortical, hippocampal and cerebellar neurons

被引:85
作者
Poulsen, CF
Simeone, TA
Maar, TE
Smith-Swintosky, V
White, HS
Schousboe, A
机构
[1] Danish Univ Pharmaceut Sci, Dept Pharmacol, DK-2100 Copenhagen, Denmark
[2] Univ Utah, Dept Pharmacol & Toxicol, Program Neurosci, Salt Lake City, UT 84112 USA
[3] Johnson & Johnson Pharmaceut Res & Dev LLC, CNS Res, Drug Discovery, Spring House, PA USA
关键词
desensitization; receptors; glutamate; N-methyl-D-aspartate; NMDA;
D O I
10.1023/B:NERE.0000010456.92887.3b
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
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 muM, 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.
引用
收藏
页码:275 / 282
页数:8
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