Excitatory and inhibitory amino acids in seizure mechanisms of El mice

近交突变El小鼠在折腾刺激下极易发生惊厥发作。在这项研究中，使用灌注系统研究了非刺激和刺激El小鼠[El(-), El(+)]和没有抽搐倾向的ddY小鼠对[^3H]天冬氨酸（Asp）（兴奋性氨基酸）和[^3H]牛磺酸（抑制性氨基酸）进入和从大脑神经皮质片释放的情况。El（-）组的天冬氨酸摄取和释放量低于ddY组，而El（+）组的天冬氨酸摄取和释放量显著高于El（-）组。El（+）对牛磺酸的摄取低于El(-)，而ddY和El（-）对牛磺酸的摄取没有差异。El（-）的牛磺酸释放量高于ddY，而El（+）的牛磺酸释放量低于El（-）。这些结果表明，El小鼠的癫痫易感性与兴奋性含天冬氨酸神经元的加速和抑制性含牛磺酸神经元的抑制有关。[^3H]在超滤液中加入高浓度（5mM）的Asp后，在dy中Asp的释放量减少，而在El（-）中Asp的释放量增加，而在El（+）中则无影响。[^3H]在超溶液中加入高浓度的n -甲基- d -天冬氨酸（一种兴奋性NMDA受体激动剂）可显著增加El（-）的Asp释放，而在ddY和El（+）中未见影响。这些结果提示，Asp自身受体功能障碍可能与El（+）中天冬氨酸释放加速有关，而非钾依赖性释放机制可能与El（-）中Asp释放增加有关。

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(-).