Gould E M, Curto K A, Craig C R, Fleming W W, Taylor D A
Department of Pharmacology and Toxicology, West Virginia University, Morgantown 26506-9223, USA.
Brain Res. 1995 Nov 6;698(1-2):62-8. doi: 10.1016/0006-8993(95)00813-6.
The GABA receptor subtype mediating responses of cerebellar Purkinje neurons to the neurotransmitter was evaluated and compared in GEPR-9 vs. nonepileptic, genetic control GEPR-NE rats. Quantitative analysis of responses to microiontophoretically applied GABA, muscimol and baclofen indicated that the inhibitory action of GABA on cerebellar Purkinje neurons was mediated by GABAA receptors since muscimol produced responses similar to those of GABA and baclofen was without substantial electrophysiological action. In addition, Purkinje neurons in GEPR-9 animals showed a similar reduced sensitivity to both GABA and muscimol. Radioligand binding studies using the GABAA receptor selective ligand, [3H]muscimol, and the benzodiazepine receptor selective ligand, [3H]flunitrazepam, were conducted on cerebellar and cortical homogenates from GEPR 9, GEPR-NE and Sprague-Dawley rats. No differences in the Kd or Bmax for these ligands among the three groups studied were observed. The lack of significant changes in the Kd and Bmax for these two ligands in the cerebellum suggests that the mechanism for the observed subsensitivity to GABA in the GEPR 9 rat lies beyond the level of the receptor, perhaps at the signal transduction process for GABA mediated inhibitory responses.
在遗传性癫痫易感大鼠（GEPR-9）与非癫痫性遗传对照大鼠（GEPR-NE）中，对介导小脑浦肯野神经元对神经递质反应的GABA受体亚型进行了评估和比较。对微量离子导入法施加的GABA、蝇蕈醇和巴氯芬反应的定量分析表明，GABA对小脑浦肯野神经元的抑制作用是由GABAA受体介导的，因为蝇蕈醇产生的反应与GABA相似，而巴氯芬没有明显的电生理作用。此外，GEPR-9动物的浦肯野神经元对GABA和蝇蕈醇的敏感性均降低。使用GABAA受体选择性配体[3H]蝇蕈醇和苯二氮䓬受体选择性配体[3H]氟硝西泮，对GEPR 9、GEPR-NE和Sprague-Dawley大鼠的小脑和皮质匀浆进行了放射性配体结合研究。在所研究的三组中，未观察到这些配体的解离常数（Kd）或最大结合容量（Bmax）存在差异。小脑这两种配体的Kd和Bmax没有显著变化，这表明GEPR 9大鼠中观察到的对GABA敏感性降低的机制可能超出了受体水平，也许在于GABA介导的抑制反应的信号转导过程。
