REDUCTION OF FUNCTIONAL GABA_A RECEPTOR EXPRESSION IN THE NEOCORTEX OF EL MICE

有大量证据表明γ-氨基丁酸（GABA）在癫痫发生中起着至关重要的作用。El（癫痫样）小鼠是从ddY小鼠开发的癫痫模型，并且非常容易癫痫发作。已经发现El小鼠表现出GABA介导的抑制的降低。然而，以往关于GABA受体功能与癫痫发生关系的研究仍停留在核心阶段。本研究以18-20周龄未受刺激的E1小鼠和ddY对照小鼠为研究对象，研究了GABA_A受体基因在新皮层中的表达和功能。1）北方印迹分析表明，E1小鼠GABA_A受体α1亚基mRNA水平较ddY小鼠降低了30%。2）利用爪蟾卵母细胞表达系统检测GABA_A受体诱导电流，分析GABA_A受体功能。注射E1小鼠新皮质mRNA的卵母细胞获得的GABA诱导电流最大值显著小于注射ddY小鼠新皮质mRNA的卵母细胞获得的GABA诱导电流最大值（荷包牡丹碱：BMI和印防己毒素：PTX）引起的场电位变化显著降低BMI和PTX引起的El（-）场电位振幅变化这些结果提示，E1（-）小鼠新皮层GABA_A受体表达减少，GABA能抑制反复发生，这可能与E1品系小鼠癫痫的发生有关。

There is extensive evidence indicating a crucial role for γ-aminobutyric acid (GABA) in epileptogenesis. The El (epilepsy-like) mouse is an epilepsy model developed from the ddY mouse and is very susceptible to seizure. El mice have been found to exhibit a decrease in GABA-mediated inhibition. However, previous studies remained nuclear about relationship between the GABA receptor function and epileptogenesis. In the present study, we investigated the GABA_A receptor gene expression and function in the neocortex of unstimulated El mice and ddY control mice (18-20 weeks old).1) Northern blot analysis showed 30% decrease in GABA_A receptor α1 subunit messenger RNA (mRNA) level in El mice, compared to ddY mice. On the other hand, β2 and γ2 subunit mRNA levels did not show any significant differences.2) GABA_A receptor functions were analyzed by the measurement of GABA-induced currents using Xenopus oocytes expression system. The maximal GABA-induced currents obtained from oocytes injected with neocortex mRNA of El mice, were significantly smaller than those obtained from oocytes injected with mRNA of ddY mice.3) Extracellular recordings from the neocortex slices using single-pulse configuration showed significant difference in the GABA_A receptor antagonist (bicuculline: BMI and picrotoxin:PTX)-induced changes of field significant decrease in the BMI and PTX-induced changes of the amplitude of field potentials in El(-) mice.These results suggest that, in the neocortex of El(-) mice, there is a decrease in GABA_A receptor expression and recurrent GABAergic inhibition, which may be related to the epileptogenesis in the El strain.