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在表达来自用FG 7142点燃的小鼠皮质mRNA的非洲爪蟾卵母细胞中的海人酸、GABAA和NMDA受体

Kainate, GABAA and NMDA receptors in Xenopus oocytes expressing mRNA from the cortex of mice kindled with FG 7142.

作者信息

Lewin E, Bleck V

机构信息

Veterans Affairs Medical Center, Denver, CO 80220, USA.

出版信息

Brain Res Mol Brain Res. 1996 Apr;37(1-2):304-8. doi: 10.1016/0169-328x(95)00338-s.

Abstract

The repeated administration of the beta-carboline, FG 7142, to mice leads to 'chemical kindling', i.e., the development of seizures following doses which were initially insufficient to produce convulsive activity. Messenger RNA (mRNA) was prepared from the cortex of control and FG 7142-treated mice killed at 10-12 days or at 28-45 days after the last kindling injection, and this mRNA was injected into Xenopus oocytes. At 3-4 days following injection, a voltage clamp technique was used to record responses to kainic acid, gamma-aminobutyric acid (GABA), and N-methyl-D-aspartate (NMDA). Kainate was significantly more potent in oocytes expressing mRNA from kindled mice killed at either 10-12 or 28-45 days than in those injected with control mRNA. GABA also was more potent in oocytes with mRNA from kindled mice killed at 10-12 days, but this difference was not present at the longer interval. Chemical kindling did not change the response to NMDA. The current-voltage relation for kainate responses was linear, and plots from kindled and control mRNA were similar. The persistent increase in potency of kainate, an excitatory glutamate ligand, may play a role in producing the lowered FG 7142 threshold characteristic of kindled mice.

摘要

向小鼠反复注射β-咔啉FG 7142会导致“化学点燃”,即最初不足以产生惊厥活动的剂量在后续给药后会引发癫痫发作。在末次点燃注射后10 - 12天或28 - 45天处死的对照小鼠和经FG 7142处理的小鼠的大脑皮层中提取信使核糖核酸(mRNA),并将该mRNA注射到非洲爪蟾卵母细胞中。注射后3 - 4天,采用电压钳技术记录对 kainic 酸、γ-氨基丁酸(GABA)和 N-甲基-D-天冬氨酸(NMDA)的反应。在表达10 - 12天或28 - 45天处死的点燃小鼠的mRNA的卵母细胞中, kainate 的效力显著高于注射对照mRNA的卵母细胞。在表达10 - 12天处死的点燃小鼠的mRNA的卵母细胞中,GABA的效力也更高,但在较长时间间隔后这种差异不存在。化学点燃并未改变对NMDA的反应。kainate反应的电流-电压关系呈线性,点燃小鼠和对照小鼠mRNA的曲线相似。兴奋性谷氨酸配体 kainate 效力的持续增加可能在产生点燃小鼠降低的FG 7142阈值特征中起作用。

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