Saenz del Burgo Laura, Cortes Roser, Mengod Guadalupe, Zarate Jon, Echevarria Enrique, Salles Joan
Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country UPV-EHU, E-01006 Vitoria, Spain.
J Comp Neurol. 2008 Oct 20;510(6):581-606. doi: 10.1002/cne.21810.
G-protein inwardly rectifying potassium (GIRK) channels mediate the synaptic actions of numerous neurotransmitters in the mammalian brain and play an important role in the regulation of neuronal excitability in most brain regions through activation of various G-protein-coupled receptors such as the serotonin 5-HT(1A) receptor. In this report we describe the localization of GIRK1, GIRK2, and GIRK3 subunits and 5-HT(1A) receptor in the rat brain, as assessed by immunohistochemistry and in situ hybridization. We also analyze the co-expression of GIRK subunits with the 5-HT(1A) receptor and cell markers of glutamatergic, gamma-aminobutyric acid (GABA)ergic, cholinergic, and serotonergic neurons in different brain areas by double-label in situ hybridization. The three GIRK subunits are widely distributed throughout the brain, with an overlapping expression in cerebral cortex, hippocampus, paraventricular nucleus, supraoptic nucleus, thalamic nuclei, pontine nuclei, and granular layer of the cerebellum. Double-labeling experiments show that GIRK subunits are present in most of the 5-HT(1A) receptor-expressing cells in hippocampus, cerebral cortex, septum, and dorsal raphe nucleus. Similarly, GIRK mRNA subunits are found in glutamatergic and GABAergic neurons in hippocampus, cerebral cortex, and thalamus, in cholinergic cells in the nucleus of vertical limb of the diagonal band, and in serotonergic cells in the dorsal raphe nucleus. These results provide a deeper knowledge of the distribution of GIRK channels in different cell subtypes in the rat brain and might help to elucidate their physiological roles and to evaluate their potential involvement in human diseases.
G蛋白内向整流钾通道（GIRK）介导哺乳动物大脑中多种神经递质的突触作用，并通过激活各种G蛋白偶联受体（如5-羟色胺5-HT(1A)受体）在大多数脑区神经元兴奋性调节中发挥重要作用。在本报告中，我们描述了通过免疫组织化学和原位杂交评估的大鼠脑中GIRK1、GIRK2和GIRK3亚基以及5-HT(1A)受体的定位。我们还通过双标记原位杂交分析了不同脑区中GIRK亚基与5-HT(1A)受体以及谷氨酸能、γ-氨基丁酸（GABA）能、胆碱能和5-羟色胺能神经元的细胞标志物的共表达情况。这三种GIRK亚基广泛分布于整个大脑，在大脑皮层、海马体、室旁核、视上核、丘脑核、脑桥核和小脑颗粒层中存在重叠表达。双标记实验表明，GIRK亚基存在于海马体、大脑皮层、隔区和中缝背核中大多数表达5-HT(1A)受体的细胞中。同样，在海马体、大脑皮层和丘脑中的谷氨酸能和GABA能神经元、斜角带垂直支核中的胆碱能细胞以及中缝背核中的5-羟色胺能细胞中也发现了GIRK mRNA亚基。这些结果为深入了解大鼠脑中不同细胞亚型中GIRK通道的分布提供了依据，并可能有助于阐明它们的生理作用以及评估它们在人类疾病中的潜在参与情况。
