During M J, Ryder K M, Spencer D D
Department of Surgery, Yale University School of Medicine, Connecticut 06510, USA.
Nature. 1995 Jul 13;376(6536):174-7. doi: 10.1038/376174a0.
Electrophysiological studies of human temporal-lobe epilepsy suggest that a loss of hippocampal GABA-mediated inhibition may underlie the neuronal hyperexcitability. However, GABA (gamma-aminobutyric acid)-containing cells are preserved and GABA receptors are maintained in the surviving hippocampal neurons. Diminished GABA release may therefore mediate the loss of inhibition. Here we show that, in the human brain, potassium-stimulated release of GABA was increased, and glutamate-induced, calcium-independent release of GABA was markedly decreased, in epileptogenic hippocampi, in contrast with contralateral, non-epileptogenic hippocampi. The glutamate-induced GABA release in vivo was transporter-mediated in rats. Furthermore, in amygdala-kindled rats, a model for human epilepsy, a decrease in glutamate-induced GABA release was associated with a 48% decrease in the number of GABA transporters. These data suggest that temporal-lobe epilepsy is characterized in part by a loss of glutamate-stimulated GABA release that is secondary to a reduction in the number of GABA transporters.
对人类颞叶癫痫的电生理研究表明，海马体中γ-氨基丁酸（GABA）介导的抑制作用丧失可能是神经元过度兴奋的基础。然而，含GABA的细胞得以保留，且存活的海马体神经元中GABA受体也得以维持。因此，GABA释放减少可能介导了抑制作用的丧失。我们在此表明，在人类大脑中，与对侧非致痫性海马体相比，致痫性海马体中钾刺激引起的GABA释放增加，而谷氨酸诱导的、不依赖钙的GABA释放则显著减少。在大鼠体内，谷氨酸诱导的GABA释放是由转运体介导的。此外，在人类癫痫模型杏仁核点燃大鼠中，谷氨酸诱导的GABA释放减少与GABA转运体数量减少48%有关。这些数据表明，颞叶癫痫的部分特征是谷氨酸刺激的GABA释放丧失，这是由于GABA转运体数量减少所致。
