Distribution and phenotype of neurons containing the ATP-sensitive K+ channel in rat brain

Distribution and phenotype of neurons containing the ATP-sensitive K+ channel in rat brain
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DOI:
10.1016/s0006-8993(98)00956-1
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发表时间:
1998-12-14
期刊:
影响因子:
2.9
通讯作者:
Levin, BE
Levin, BE
中科院分区:
医学3区
文献类型:
--
作者:
Dunn-Meynell, AA;Rawson, NE;Levin, BE

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当周围的血糖水平发生变化时,大脑中特定的神经元群会改变它们的放电率。这些对葡萄糖反应的神经元被整合到控制体内能量平衡的系统中。它们含有一个ATP敏感的K+通道(K-ATP)来调节这一反应。K-ATP通道由一个内向整流型成孔单元(KIR(6.1)或KIR(6.2))和一个磺酰基脲结合部位组成。在这里,我们用原位杂交和免疫细胞化学相结合的方法研究了大鼠脑内含有Kir(6.2)mRNA的细胞的解剖分布和表型。含有KIR(6.2)信使核糖核酸的细胞广泛分布于大脑各处,在已知含有特定葡萄糖反应神经元的区域没有明显的浓度。神经元表达神经元特异性烯醇化酶、酪氨酸羟基酶、神经肽Y(NPY)和谷氨酸脱羧酶亚型GAD(65)。未见表达胶质纤维酸性蛋白的星形胶质细胞和表达碳酸氢酶II的少突胶质细胞共表达Kir(6.2)mRNA。几乎所有下丘脑弓状核的NPY神经元和黑质、致密部和蓝斑的儿茶酚胺神经元都含有KIR(6.2)mRNA。肾上腺素能神经元在C2区也高表达KIR(6.2),而去甲肾上腺素能神经元在A5和A2区表达较低。Kir(6.2)mRNA的广泛分布表明,K-ATP通道可能在神经元中发挥神经保护作用,而这些神经元并不直接参与整合与身体能量平衡相关的信号。(C)1998 Elsevier Science B.V.保留所有权利。
Select groups of neurons within the brain alter their firing rate when ambient glucose levels change. These glucose-responsive neurons are integrated into systems which control energy balance in the body. They contain an ATP-sensitive K+ channel (K-ATP) which mediates this response. K-ATP channels are composed of an inwardly rectifying pore-forming unit (Kir(6.1) or Kir(6.2)) and a sulfonylurea binding site. Here, we examined the anatomical distribution and phenotype of cells containing Kir(6.2) mRNA within the rat brain by combinations of in situ hybridization and immunocytochemistry. Cells containing Kir(6.2) mRNA were widely distributed throughout the brain without apparent concentration in areas known to contain specific glucose-responsive neurons. Kir(6.2) mRNA was present in neurons expressing neuron-specific enolase, tyrosine hydroxylase, neuropeptide Y (NPY) and the glutamic acid decarboxylase isoform, GAD(65). No astrocytes expressing glial fibrillary acidic protein or oligodendrocytes expressing carbonic anhydrase II were found to co-express Kir(6.2) mRNA. Virtually all of the NPY neurons in the hypothalamic arcuate n. and catecholamine neurons in the substantia nigra, pars compacta and locus coeruleus contained Kir(6.2) mRNA. Epinephrine neurons in the C2 area also expressed high levels of Kir(6.2) while noradrenergic neurons in A5 and A2 areas expressed lower levels. The widespread distribution of Kir(6.2) mRNA suggests that the K-ATP channel may serve a neuroprotective role in neurons which are not directly involved in integrating signals related to the body's energy homeostasis. (C) 1998 Elsevier Science B.V. All rights reserved.