Claudio O I, Ferchmin P, Velísek L, Sperber E F, Moshé S L, Ortiz J G
Department of Pharmacology and Toxicology, University of Puerto Rico, School of Medicine, San Juan 00936-5067, USA.
Epilepsia. 2000;41 Suppl 6:S104-10. doi: 10.1111/j.1528-1157.2000.tb01567.x.
To examine the relationship between seizures and excitatory amino acid transporter (EAAT) activity and whether up-regulation of EAAT activity alters epileptogenicity.
In this study, we exposed rat hippocampal slices to different convulsants before measuring EAAT activity. Rats were exposed to the EAAT inhibitor pyrrolidine-2,4-dicarboxylic acid (PDC) before entorhinal cortex/hippocampal slices were obtained. These slices were exposed to low-Mg2+ buffer while electrophysiological recordings were obtained from the entorhinal cortex. mGluR III acting agents were used to study whether activation of mGluR III could regulate EAAT activity and if this regulation could overcome the effects on EAAT activity induced by the convulsants.
Veratridine, kainic acid (KA), and pilocarpine reduced EAAT activity in rat hippocampal slices. L-2-Amino-4-phosphonobutyric acid (an mGluR III agonist) restored EAAT activity and reduced epileptiform activity to near control levels. The saturation curve for glutamate uptake in slices from KA-seized rats killed 2 hours after the first forelimb clonus was displaced to the left, suggesting a compensatory change for the enhanced excitation. On the other hand, rats injected with the EAAT inhibitor PDC (by intracerebroventricular injection) had more severe KA-induced seizures and N-methyl-D-aspartate epileptiform activity than control rats. Furthermore, hippocampal slices from KA- or KA+PDC-treated rats exposed to low Mg2+ reduced their firing rate to nearly zero once they returned to normal solution, whereas their control counterparts continued to fire, although at a lower rate.
These results suggest a significant contribution of EAATs in some experimental epilepsy models and point to their short-term regulation by mGluR III as a possible source of their plasticity.
研究癫痫发作与兴奋性氨基酸转运体（EAAT）活性之间的关系，以及EAAT活性上调是否会改变致痫性。
在本研究中，我们在测量EAAT活性之前，将大鼠海马脑片暴露于不同的惊厥剂。在获取内嗅皮质/海马脑片之前，大鼠先暴露于EAAT抑制剂吡咯烷-2,4-二羧酸（PDC）。这些脑片暴露于低镁缓冲液中，同时从内嗅皮质进行电生理记录。使用代谢型谷氨酸受体III（mGluR III）作用剂来研究mGluR III的激活是否能调节EAAT活性，以及这种调节是否能克服惊厥剂对EAAT活性的影响。
藜芦碱、红藻氨酸（KA）和毛果芸香碱降低了大鼠海马脑片中的EAAT活性。L-2-氨基-4-膦酰丁酸（一种mGluR III激动剂）恢复了EAAT活性，并将癫痫样活动降低至接近对照水平。首次前肢阵挛发作后2小时处死的KA致痫大鼠脑片中谷氨酸摄取的饱和曲线向左移位，提示对增强的兴奋有代偿性变化。另一方面，经脑室注射EAAT抑制剂PDC的大鼠比对照大鼠有更严重的KA诱导的癫痫发作和N-甲基-D-天冬氨酸癫痫样活动。此外，暴露于低镁环境的KA或KA+PDC处理大鼠的海马脑片，一旦恢复到正常溶液中，其放电频率几乎降至零，而对照脑片尽管放电频率较低，但仍继续放电。
这些结果表明EAATs在某些实验性癫痫模型中起重要作用，并指出mGluR III对其短期调节可能是其可塑性的一个来源。
