Brünig I, Sommer M, Hatt H, Bormann J
Ruhr-Universität Bochum, Lehrstuhl für Zellphysiologie, D-44780 Bochum, Germany.
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2456-60. doi: 10.1073/pnas.96.5.2456.
The gamma-aminobutyric acid type A (GABAA) receptor is the predominant Cl- channel protein mediating inhibition in the olfactory bulb and elsewhere in the mammalian brain. The olfactory bulb is rich in neurons containing both GABA and dopamine. Dopamine D1 and D2 receptors are also highly expressed in this brain region with a distinct and complementary distribution pattern. This distribution suggests that dopamine may control the GABAergic inhibitory processing of odor signals, possibly via different signal-transduction mechanisms. We have observed that GABAA receptors in the rat olfactory bulb are differentially modulated by dopamine in a cell-specific manner. Dopamine reduced the currents through GABA-gated Cl- channels in the interneurons, presumably granule cells. This action was mediated via D1 receptors and involved phosphorylation of GABAA receptors by protein kinase A. Enhancement of GABA responses via activation of D2 dopamine receptors and phosphorylation of GABAA receptors by protein kinase C was observed in mitral/tufted cells. Decreasing or increasing the binding affinity for GABA appears to underlie the modulatory effects of dopamine via distinct receptor subtypes. This dual action of dopamine on inhibitory GABAA receptor function in the rat olfactory bulb could be instrumental in odor detection and discrimination, olfactory learning, and ultimately odotopic memory formation.
γ-氨基丁酸A型（GABAA）受体是介导嗅球及哺乳动物脑内其他部位抑制作用的主要氯离子通道蛋白。嗅球富含同时含有γ-氨基丁酸（GABA）和多巴胺的神经元。多巴胺D1和D2受体在该脑区也高度表达，呈现出独特且互补的分布模式。这种分布表明多巴胺可能通过不同的信号转导机制控制气味信号的GABA能抑制性处理。我们观察到，大鼠嗅球中的GABAA受体受多巴胺以细胞特异性方式进行差异性调节。多巴胺降低了中间神经元（可能是颗粒细胞）中通过GABA门控氯离子通道的电流。该作用通过D1受体介导，涉及蛋白激酶A对GABAA受体的磷酸化。在二尖瓣/簇状细胞中观察到，通过激活D2多巴胺受体增强GABA反应以及蛋白激酶C对GABAA受体的磷酸化。多巴胺通过不同受体亚型产生的调节作用似乎是基于对GABA结合亲和力的降低或增加。多巴胺对大鼠嗅球中抑制性GABAA受体功能的这种双重作用可能有助于气味检测与辨别、嗅觉学习以及最终的气味定位记忆形成。
