Dopamine D2 receptor mediated presynaptic inhibition of striatopallidal GABAA IPSCs in vitro
Dopamine D2 receptor mediated presynaptic inhibition of striatopallidal GABAA IPSCs in vitro
复制标题
DOI：
10.1016/s0028-3908(01)00038-7
复制
发表时间：
2001-07-01
影响因子：
4.7
通讯作者：
Stanford, IM
中科院分区：
文献类型：
--
作者：
Cooper, AJ;Stanford, IM
用全细胞膜片钳技术研究了多巴胺对苍白球内GABA释放的调节作用。在矢状切片中，纹状体中的单次电击电刺激诱发GABA（A）抑制性突触后电流（IPSC），其以剂量依赖性方式（0.3-30 μ M）被多巴胺抑制，IC 50值为0.7 μ M。抑制伴随着成对脉冲易化的增加，表明突触前效应。在冠状切片中，在邻近记录位点的GP内的刺激诱发GABA（A）IPSC，其相对不受多巴胺的影响，表明缺乏对来自局部GP轴突侧支末端的GABA释放的调节。未观察到保持电流、膜电位、放电率或自发IPSCs频率的一致变化。在氯化物负载的细胞中记录到抗河豚毒素的微型（m）IPSCs。多巴胺（3-30 μ M）降低mIPSC的频率，但对mIPSC振幅没有影响，证实了突触前效应。添加“D2样”激动剂喹吡罗（3 μ M）而不是“D1样”激动剂SKF 38393（10 μ M）模拟了这些作用。“D2样”拮抗剂舒必利（10 μ M），而单独使用没有效果。阻断了多巴胺的作用。多巴胺D_4选择性拮抗剂L745，870（1 μ M）或D_1选择性拮抗剂SCH 23390（10 μ M）则无此作用。多巴胺耗竭后这种机制的减弱可能有助于在帕金森病动物模型中观察到的CP神经元活性的变化。(C)2001爱思唯尔科技有限公司版权所有。
The modulation of GABA release within the globus pallidus (GP) by dopamine was studied using whole-cell patch clamp recordings from visually identified neurones. In sagittal slices, single shock electrical stimulation in the striatum evoked GABA(A) inhibitory postsynaptic currents (IPSCs), which were inhibited by dopamine in a dose-dependent manner (0.3-30 muM) with an IC50 value of 0.7 muM. The inhibition was accompanied by an increase in paired pulse facilitation, indicative of a presynaptic effect. In coronal slices, stimulation within the GP adjacent to the recording site evoked GABA(A) IPSCs which were relatively unaffected by dopamine indicating the lack of modulation of GABA release from terminals of local GP axon collaterals. No consistent changes in holding current, membrane potential, firing rate or the frequency of spontaneous IPSCs was observed.Tetrodotoxin-resistant miniature (m)IPSCs were recorded in chloride-loaded cells. Dopamine (3-30 muM) reduced the frequency of mIPSCs, but was without effect on mIPSC amplitude, confirming a presynaptic effect. The addition of the 'D2 like' agonist quinpirole (3 muM), but not the 'D1 like' agonist SKF 38393 (10 muM), mimicked these effects. The 'D2 like' antagonist sulpiride (10 muM), while having no effect alone. blocked the action of dopamine. In contrast the dopamine D4 selective antagonist L745, 870 (1 muM) or D1 antagonist SCH 23390 (10 muM) were without effect.These results indicate that dopamine acts on presynaptic D2 receptors on striatopallidal terminals to reduce the release of GABA in the GP. Attenuation of this mechanism following the depletion of dopamine may contribute to the changes in CP neuronal activity observed in animal models of Parkinson's disease. (C) 2001 Elsevier Science Ltd. All rights reserved.