Poulsen Claus F, Simeone Timothy A, Maar Thomas E, Smith-Swintosky Virginia, White H Steven, Schousboe Arne
Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark.
Neurochem Res. 2004 Jan;29(1):275-82. doi: 10.1023/b:nere.0000010456.92887.3b.
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.
在由大脑皮层、海马体和小脑的神经元组成的不同细胞培养系统中，研究了抗癫痫药物托吡酯对通过（RS）-2-氨基-3-（3-羟基-5-甲基异恶唑-4-基）丙酸（AMPA）和海人藻酸（KA）受体的Ca2+摄取的影响。使用荧光Ca2+螯合剂监测细胞内Ca2+浓度的变化来测定Ca2+内流，或用钴染色来评估托吡酯对Ca2+通透型AMPA/KA受体的影响。在所有研究的神经元培养类型中，发现AMPA和KA在一部分神经元群体中引发Ca2+内流。浓度为30和100微摩尔的托吡酯可将Ca2+内流抑制高达60%。AMPA和KA诱发的Ca2+内流的调节可能有助于托吡酯的抗癫痫和神经保护特性。
