Kirchner Anne, Breustedt Jorg, Rosche Berit, Heinemann Uwe F, Schmieden Volker
Johannes Müller Institut für Physiologie, Universitätsklinikum Charité, Humboldt Universität, Berlin, Germany.
Epilepsia. 2003 Sep;44(9):1145-52. doi: 10.1046/j.1528-1157.2003.01603.x.
The imbalance between neuronal inhibition and excitation contributes to epileptogenesis. Inhibition in the central nervous system (CNS) is mediated by gamma-aminobutyric acid (GABA) and glycine. Recent studies indicate the expression of glycine receptor (GlyR) in hippocampus and neocortex. However, the function of GlyR in these regions is not clarified completely. The aim of this study was to investigate whether the GlyR agonists glycine and taurine promote an anticonvulsive effect.
We induced epileptiform discharges by reducing extracellular Mg2+ concentration in combined rat entorhinal cortex-hippocampal slices (400 micro m). Epileptiform discharges were detected by using extracellular recording techniques.
Seizure-like events were suppressed by taurine, exhibiting a half-maximal inhibitory effect (IC50) of 0.9 mM. Suppression of late recurrent discharges in the medial entorhinal cortex and recurrent short discharges in the hippocampus was obtained at an IC50 value of 1.6 and 2.1 mM, respectively. Strychnine at concentrations <1 micro M abolished these effects. Likewise glycine, after an initial proconvulsant effect, suppressed epileptiform discharges.
These findings show that GlyR agonists, in particular taurine, could serve as potential anticonvulsants and suggest an important role of GlyR in cortical function and dysfunction.
神经元抑制与兴奋之间的失衡有助于癫痫的发生。中枢神经系统（CNS）中的抑制作用由γ-氨基丁酸（GABA）和甘氨酸介导。最近的研究表明甘氨酸受体（GlyR）在海马体和新皮层中表达。然而，GlyR在这些区域的功能尚未完全阐明。本研究的目的是探讨GlyR激动剂甘氨酸和牛磺酸是否具有抗惊厥作用。
我们通过降低联合的大鼠内嗅皮层-海马切片（400μm）中的细胞外镁离子浓度来诱导癫痫样放电。使用细胞外记录技术检测癫痫样放电。
牛磺酸可抑制癫痫样事件，半数最大抑制效应（IC50）为0.9 mM。在内侧内嗅皮层中抑制晚期复发放电以及在海马体中抑制复发短程放电的IC50值分别为1.6 mM和2.1 mM。浓度<1μM的士的宁可消除这些作用。同样，甘氨酸在最初的促惊厥作用后，可抑制癫痫样放电。
这些发现表明GlyR激动剂，尤其是牛磺酸，可作为潜在的抗惊厥药物，并提示GlyR在皮层功能和功能障碍中起重要作用。
