Excitatory and inhibitory amino acids in seizure mechanisms of El mice

近交突变El小鼠在抛掷刺激时对惊厥性发作高度敏感。在这项研究中，使用灌注系统研究了未受刺激和受刺激的El小鼠[El（-），El（+）]和ddY小鼠（没有惊厥倾向）对[^3H]天冬氨酸（Asp）（一种兴奋性氨基酸）和[^3H]牛磺酸（一种抑制性氨基酸）在大脑神经皮层切片中的摄取和释放。E1（-）中天冬氨酸的吸收和释放低于ddY，E1（+）中天冬氨酸的吸收和释放显著高于E1（-）。El（+）中的牛磺酸摄取低于El（-），尽管在ddY和El（-）之间没有发现摄取差异。El（-）中的牛磺酸释放高于ddY，而El（+）中的牛磺酸释放低于El（-）。这些结果表明，兴奋性天冬氨酸神经元的加速和抑制性牛磺酸神经元的抑制参与了癫痫易感性在El小鼠。灌流液中加入高浓度（5 mM）Asp，ddY细胞[^3H]Asp释放量减少，而El（-）细胞[^3H]Asp释放量增加，El（+）细胞[^3H]Asp释放量无明显变化。高浓度兴奋性NMDA受体激动剂N-甲基-D-天冬氨酸（N-methyl-D-aspartate）灌流液可显著增加E1（-）细胞[^3H]Asp的释放，而ddY和E1（+）细胞则无此作用。提示E1（+）时天冬氨酸自身受体功能障碍可能与天冬氨酸释放加快有关，E1（-）时天冬氨酸释放增加可能与非钾依赖性释放机制有关。

Inbred mutant El mice are highly suscrptible to convulsive seizures upon tossing stimulation. In this study, uptake and release of [^3H]aspartate(Asp), an excitatory amino acid, and [^3H]taurine, an inhibitory amino acid, into and from cerebral neurocortical slices using a perfusion system were investigated in both nonstimulated and stimulated El mice [El(-), El(+)] and in ddY mice, which do not have a convulsive disposition. Aspartate uptake and release in El(-) were lower than in ddY, and these in El(+) were significantly higher than in El(-). Taurine uptake in El(+) was lower than El(-), though no difference in uptake was found between ddY and El(-). Taurine release in El(-) was higher than ddY whereas the release in El(+) was lower than in El(-). These results suggest that acceleration of excitatory aspartate containing neurons and also suppression of inhibitory taurine containing neurons are involved in the seizure susceptibility in the El mice. [^3H]Asp release was decreased in ddY, when highe concentration (5mM) Asp was added in the superfusing solution, whereas it was increased in El(-) and no effect was observed in El(+). [^3H]Asp release was significantly increased in El(-), when high concentration of N-methyl-D-aspartate, an agonist of excitatory NMDA receptor, was added in the superfusing solution, whereas no effect was observed in ddY and El(+). These findings suggest that dysfunction of auto-receptor for Asp may relate to accelarated aspartate release in El(+), and that non-potassium depended release mechanism may concern to the increased release of Asp in El(-).