首页> 美国卫生研究院文献>The Journal of Neuroscience >Cell Type-Specific Differences in Chloride-Regulatory Mechanisms and GABAA Receptor-Mediated Inhibition in Rat Substantia Nigra
【2h】

Cell Type-Specific Differences in Chloride-Regulatory Mechanisms and GABAA Receptor-Mediated Inhibition in Rat Substantia Nigra

机译:大鼠黑质中氯化物调节机制和GABA A受体介导的抑制的细胞类型特异性差异。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

The regulation of intracellular chloride has important roles in neuronal function, especially by setting the magnitude and direction of the Cl- flux gated by GABAA receptors. Previous studies have shown that GABAA-mediated inhibition is less effective in dopaminergic than in GABAergic neurons in substantia nigra. We studied whether this phenomenon may be related to a difference in Cl-regulatory mechanisms. Light-microscopic immunocytochemistry revealed that the potassium-chloride cotransporter 2 (KCC2) was localized only in the dendrites of nondopaminergic (primarily GABAergic) neurons in the substantia nigra, whereas the voltage-sensitive chloride channel 2 (ClC-2) was observed only in the dopaminergic neurons of the pars compacta. Electron-microscopic immunogold labeling confirmed that KCC2 is localized in the dendritic plasma membrane of GABAergic neurons close to inhibitory synapses. Confocal microscopy showed that ClC-2 was selectively expressed in the somatic and dendritic cell membranes of the dopaminergic neurons. Gramicidin-perforated-patch recordings revealed that the GABAA IPSP reversal potential was significantly less negative and had a much smaller hyperpolarizing driving force in dopaminergic than in GABAergic neurons. The GABAA reversal potential was significantly less negative in bicarbonate-free buffer in dopaminergic but not in GABAergic neurons. The present study suggests that KCC2 is responsible for maintaining the low intracellular Cl- concentration in nigral GABAergic neurons, whereas a sodium-dependent anion (Cl--HCO3-) exchanger and ClC-2 are likely to serve this role in dopaminergic neurons. The relatively low efficacy of GABAA-mediated inhibition in nigral dopaminergic neurons compared with nigral GABAergic neurons may be related to their lack of KCC2.
机译:细胞内氯化物的调节在神经元功能中具有重要作用,特别是通过设置由GABAA受体控制的Cl -通量的大小和方向。先前的研究表明,在黑质中,GABAA介导的抑制作用对多巴胺能的抑制作用小于对GABA能神经元的抑制作用。我们研究了这种现象是否可能与Cl调节机制的差异有关。光学显微镜免疫细胞化学显示,氯化钾共转运蛋白2(KCC2)仅位于黑质中非多巴胺能神经元(主要是GABA能神经元)的树突中,而电压敏感的氯离子通道2(ClC-2)仅在黑质中。致密部的多巴胺能神经元。电子显微镜免疫金标记证实,KCC2位于GABA能神经元的树突质膜中,接近抑制性突触。共聚焦显微镜显示ClC-2在多巴胺能神经元的体细胞和树突状细胞膜中选择性表达。格拉米霉素穿孔的贴片记录显示,与GABA能神经元相比,多巴胺能的GABA A IPSP逆转电位明显更低,负极化力小得多。在多巴胺能神经元的无碳酸氢盐缓冲液中,GABAA逆转潜能显着降低,而在GABA能神经元中则没有。本研究表明,KCC2负责维持低水平的GABA能神经元细胞内Cl -浓度,而钠依赖性阴离子(Cl - -HCO3 - )交换子和ClC-2可能在多巴胺能神经元中发挥这种作用。与黑色素GABA能神经元相比,GABA A介导的抑制黑色素多巴胺能神经元的功效相对较低,可能与其缺乏KCC2有关。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号