Kamphuis W, Huisman E, Dreijer A M, Ghijsen W E, Verhage M, Lopes da Silva F H
Department of Experimental Zoology, University of Amsterdam, The Netherlands.
Brain Res. 1990 Mar 12;511(1):63-70. doi: 10.1016/0006-8993(90)90225-z.
The release of endogenous amino acids from hippocampal CA1 subslices under basal conditions and the release evoked by high potassium (50 mM K+) depolarization was studied during kindling epileptogenesis. Emphasis was put on the release of the amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glutamate. Kindling was induced by tetanic stimulation of the Schaffer-collaterals/commissural fibers of the dorsal hippocampus of the rat. The calcium-dependent GABA release in the presence of high K+ was significantly increased (40-46%) in fully kindled animals, 24 h after the last seizure, in comparison to controls. At long-term, 28 days after the last seizure, the calcium-dependent GABA release was still significantly increased (45-49%). An increased release of GABA in kindled animals was still found when GABA uptake was blocked by nipecotic acid. In contrast, no significant alterations were encountered in the basal or high potassium induced release of the excitatory amino acids aspartate and glutamate. These results suggest that kindling epileptogenesis is accompanied by a specific and long-lasting enhancement of GABA exocytosis which may lead to a desensitization of the GABA receptor, and thus determine the increase of seizure sensitivity.
在点燃癫痫发生过程中，研究了基础条件下海马CA1亚切片内源性氨基酸的释放以及高钾（50 mM K+）去极化诱发的释放。重点关注氨基酸神经递质γ-氨基丁酸（GABA）和谷氨酸的释放。通过强直刺激大鼠背侧海马的Schaffer侧支/联合纤维诱导点燃。与对照组相比，在最后一次癫痫发作后24小时，完全点燃的动物在高钾存在下钙依赖性GABA释放显著增加（40 - 46%）。长期来看，在最后一次癫痫发作后28天，钙依赖性GABA释放仍显著增加（45 - 49%）。当GABA摄取被哌啶酸阻断时，在点燃动物中仍发现GABA释放增加。相反，兴奋性氨基酸天冬氨酸和谷氨酸的基础释放或高钾诱导释放未出现显著改变。这些结果表明，点燃癫痫发生伴随着GABA胞吐作用的特异性和持久性增强，这可能导致GABA受体脱敏，从而决定癫痫发作敏感性的增加。
