Interaction between Ca2+, K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode
Interaction between Ca2+, K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode
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DOI：
10.1038/sj.bjp.0701941
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发表时间：
1998-07-01
影响因子：
7.3
通讯作者：
Kaneko, S
中科院分区：
文献类型：
--
作者：
Okada, M;Kawata, Y;Kaneko, S
1利用微透析谷氨酸生物传感器研究了钙离子和钾离子诱发的大鼠海马细胞外谷氨酸释放的多种成分。此外，抗癫痫药物，卡马西平（CBZ）和唑尼沙胺（ZNS）灌注通过探针对谷氨酸释放的影响进行了评估。2基础谷氨酸水平低于检测限（类似于0.1 μ M）。细胞外KCl增加（从2.7到50和100 mM）分别将细胞外海马谷氨酸水平增加到9.2 +/- 1.4和20.0 +/- 2.6 μ M，根据60 min的曲线下面积（AUC）计算。最初的短暂上升，后期的平缓上升，4细胞外CaCl 2水平的增加或去除分别增强和减少50 mM KCl诱发的海马谷氨酸释放（AUC 60分钟）从9.2 +/- 1.4到12.4 +/- 2.1和5.8 +/- 0.9 μ M。5用100 μ M CBZ或1 mM ZNS灌注抑制50 mM KCl诱发的海马谷氨酸释放（AUC 60分钟）分别从9.2 +/- 1.4至5.5 +/- 1.1和5.8 +/- 1.3 μ M，以及Ca 2+对KCl诱发的海马谷氨酸释放的刺激作用。6这些结果表明，CBZ和ZNS均可通过抑制兴奋性谷氨酸能传递减少癫痫样事件。
1 Multiple components of hippocampal glutamate release were examined by study of Ca2+- and K+-evoked hippocampal extracellular glutamate release using an in vivo microdialysis glutamate biosensor in urethane-anaesthetized rats. In addition, the effects of the antiepileptic drugs, carbamazepine (CBZ) and zonisamide (ZNS) perfused through the probe on glutamate release were assessed.2 Basal glutamate levels were below detection limits (similar to 0.1 mu M). An increase in extracellular KCl (from 2.7 to 50 and 100 mM) increased extracellular hippocampal glutamate levels to 9.2 +/- 1.4 and 20.0 +/- 2.6 mu M, respectively, calculated from the area under curve (AUC) for 60 min.3 This KCl-evoked glutamate release consisted of three components: an initial transient rise, a late gentle rise, and late multiple phasic transient rises.4 An increase in or removal of extracellular CaCl2 levels respectively enhanced and reduced the 50 mM KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2 +/- 1.4 to 12.4 +/- 2.1 and 5.8 +/- 0.9 mu M.5 Perfusion with 100 mu M CBZ or 1 mM ZNS inhibited both the 50 mM KCl-evoked hippocampal glutamate release (AUC for 60 min) from 9.2 +/- 1.4 to 5.5 +/- 1.1 and to 5.8 +/- 1.3 mu M, respectively, as well as the stimulatory effects of Ca2+ on KCl-evoked hippocampal glutamate release.6 These results suggest that both CBZ and ZNS may reduce epileptiform events by inhibiting excitatory glutamatergic transmission.