Ether-A -go-go 1 (Eag1) Potassium Channel Expression in Dopaminergic Neurons of Basal Ganglia is Modulated by 6-Hydroxydopamine Lesion
Ether-A -go-go 1 (Eag1) Potassium Channel Expression in Dopaminergic Neurons of Basal Ganglia is Modulated by 6-Hydroxydopamine Lesion
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DOI：
10.1007/s12640-011-9286-3
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发表时间：
2012-04-01
影响因子：
3.7
通讯作者：
Del Bel, E. A.
中科院分区：
文献类型：
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作者：
Ferreira, N. R.;Mitkovski, M.;Del Bel, E. A.
以太A go-go （Eag）基因编码电压门控钾离子通道Kv10.1，其功能仍然未知。由于多巴胺可能直接影响K+通道，我们评估了神经毒素6-羟多巴胺（6-OHDA）诱导的黑质纹状体多巴胺能损伤是否会改变大鼠基底节及相关脑区Eag1-K+通道的表达。雄性Wistar大鼠向内侧前脑束注射生理盐水或6-羟多巴胺（单侧）。6-OHDA诱导的多巴胺能损伤程度通过阿吗啡诱导的旋转行为和酪氨酸羟化酶（TH）免疫反应性来评估。6-OHDA微注射导致多巴胺能细胞部分或完全损伤，Eag1+细胞的损伤程度与损伤程度成正比。此外，我们观察到同侧纹状体中TH免疫反应性降低。总之，Eag1-K+通道在大鼠脑黑质纹状体通路中的表达，其与多巴胺能细胞的共定位及其反映病变程度的减少突出了可以研究该通道功能作用的生理回路。Eag1-K+通道在多巴胺能细胞中的表达表明，这些通道是产生和维持多巴胺能中脑神经元电生理活动模式的多种离子通道的一部分。
The ether A go-go (Eag) gene encodes the voltage-gated potassium (K+) ion channel Kv10.1, whose function still remains unknown. As dopamine may directly affect K+ channels, we evaluated whether a nigrostriatal dopaminergic lesion induced by the neurotoxin 6-hydroxydopamine (6-OHDA) would alter Eag1-K+ channel expression in the rat basal ganglia and related brain regions. Male Wistar rats received a microinjection of either saline or 6-OHDA (unilaterally) into the medial forebrain bundle. The extent of the dopaminergic lesion induced by 6-OHDA was evaluated by apomorphine-induced rotational behavior and by tyrosine hydroxylase (TH) immunoreactivity. The 6-OHDA microinjection caused a partial or complete lesion of dopaminergic cells, as well as a reduction of Eag1+ cells in a manner proportional to the extent of the lesion. In addition, we observed a decrease in TH immunoreactivity in the ipsilateral striatum. In conclusion, the expression of the Eag1-K+-channel throughout the nigrostriatal pathway in the rat brain, its co-localization with dopaminergic cells and its reduction mirroring the extent of the lesion highlight a physiological circuitry where the functional role of this channel can be investigated. The Eag1-K+ channel expression in dopaminergic cells suggests that these channels are part of the diversified group of ion channels that generate and maintain the electrophysiological activity pattern of dopaminergic midbrain neurons.