Thomzig Achim, Prüss Harald, Veh Rüdiger W
Institut für Anatomie, der Charité, Universitätsklinikum der Humboldt-Universität zu Berlin, Philippstrasse 12, D-10115 Berlin, Germany.
Brain Res. 2003 Oct 3;986(1-2):132-8. doi: 10.1016/s0006-8993(03)03222-0.
ATP-sensitive potassium channels comprise a complex of two structurally different proteins: a member of the inwardly rectifying Kir6 family (Kir6.1 or Kir6.2) and a sulfonylurea receptor (SUR1 or SUR2). Their regulation by intracellular ADP/ATP-concentrations and through various pharmacological agents has profound implications for the excitability of cells and, in the case of neurons, for neurotransmitter release. We previously showed that in rat brain, the Kir6.1 subunit is predominantly expressed in astrocytes in contrast to the Kir6.2 subunit, which is exclusively expressed in neurons. In this report we show, that in addition to the astrocytic expression, the Kir6.1 protein is also found in a small subset of neurons in distinct areas of the brain, like the hypothalamic supraoptic and paraventricular nuclei and the striatum. The Kir6.1-positive neurons in the striatum could be characterized as cholinergic interneurones, verified by immunofluorescence double staining. This complete colocalization of the Kir6.1 subunit in cholinergic interneurons is interesting with respect to the pharmacological potential of these channels. A selective modulation of the Kir6.1 subunit in the cholinergic striatal interneurons may eventually be of therapeutic value for the treatment of Parkinson's disease.
ATP敏感性钾通道由两种结构不同的蛋白质组成一个复合体:内向整流型Kir6家族的一个成员(Kir6.1或Kir6.2)和一个磺脲类受体(SUR1或SUR2)。它们受细胞内ADP/ATP浓度以及各种药物的调节,这对细胞的兴奋性具有深远影响,对于神经元而言,则对神经递质释放有深远影响。我们之前表明,在大鼠脑中,与仅在神经元中表达的Kir6.2亚基相比,Kir6.1亚基主要在星形胶质细胞中表达。在本报告中我们表明,除了星形胶质细胞表达外,在脑的不同区域,如下丘脑视上核和室旁核以及纹状体的一小部分神经元中也发现了Kir6.1蛋白。纹状体中Kir6.1阳性神经元可被鉴定为胆碱能中间神经元,这通过免疫荧光双重染色得以证实。就这些通道的药理潜力而言,Kir6.1亚基在胆碱能中间神经元中的这种完全共定位很有意思。对胆碱能纹状体中间神经元中Kir6.1亚基的选择性调节最终可能对帕金森病的治疗具有治疗价值。