Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes
Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes
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DOI：
10.1074/jbc.m405985200
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发表时间：
2004-10-15
影响因子：
4.8
通讯作者：
Kurachi, Y
中科院分区：
文献类型：
--
作者：
Hibino, H;Fujita, A;Kurachi, Y
内向整流性K+通道亚基Kir5.1在脑内大量表达，但其确切的分布和功能在很大程度上仍不清楚。由于Kir5.1和Kir4.1在视网膜神经胶质细胞中共表达，我们比较了Kir5.1和Kir4.1在小鼠脑中的生化和免疫学特性。免疫沉淀实验表明，大脑至少表达两个KIR通道亚群，异构体Kir4.1/5.1和同构体Kir4.1。使用特定抗体的免疫标记显示，包含Kir4.1和Kir5.1亚基的通道是以区域特异性的方式组装的。异构体Kir4.1/5.1存在于新皮质和嗅球的肾小球中。Hommer Kir4.1仅限于海马体和丘脑。未鉴定出同源基因Kir5.1。KIR4.1/5.1和Kir4.1的表达似乎仅在星形胶质细胞中表达，尤其是在面对软膜和血管的膜区或突触周围的突起。Kir4.1/5.1和Kir4.1都可能与含有PDZ结构域的合成素相关，这可能参与了星形胶质细胞KIR通道的亚细胞靶向。因为异构体Kir4.1/5.1和同聚体Kir4.1具有不同的离子通道性质(Tanemoto，M.，Kittaka，N.，Inanobe，A.和Kurachi，Y.(2000)J.Physiol)。(Lond.)525,587-592和Tucker，S.J.，Imbrici，P.，Salatore，L.，D‘Adamo，M.C.和Pessia，M.(2000)J.Biol。化学。16404-16407)，这些通道可能在脑星形胶质细胞的K+缓冲作用中以区域特异性的方式发挥不同的生理作用。
The inwardly rectifying K+ channel subunit Kir5.1 is expressed abundantly in the brain, but its precise distribution and function are still largely unknown. Because Kir5.1 is co-expressed with Kir4.1 in retinal glial Muller cells, we have compared the biochemical and immunological properties of Kir5.1 and Kir4.1 in the mouse brain. Immunoprecipitation experiments suggested that brain expressed at least two subsets of Kir channels, heteromeric Kir4.1/5.1 and homomeric Kir4.1. Immunolabeling using specific antibodies showed that channels comprising Kir4.1 and Kir5.1 subunits were assembled in a region-specific fashion. Heteromeric Kir4.1/5.1 was identified in the neocortex and in the glomeruli of the olfactory bulb. Homomeric Kir4.1 was confined to the hippocampus and the thalamus. Homomeric Kir5.1 was not identified. Kir4.1/5.1 and Kir4.1 expression appeared to occur only in astrocytes, specifically in the membrane domains facing the pia mater and blood vessels or in the processes surrounding synapses. Both Kir4.1/5.1 and Kir4.1 could be associated with PDZ domain-containing syntrophins, which might be involved in the subcellular targeting of these astrocyte Kir channels. Because heteromeric Kir4.1/5.1 and homomeric Kir4.1 have distinct ion channel properties (Tanemoto, M., Kittaka, N., Inanobe, A., and Kurachi, Y. (2000) J. Physiol. (Lond.) 525, 587-592 and Tucker, S. J., Imbrici, P., Salvatore, L., D'Adamo, M. C., and Pessia, M. (2000) J. Biol. Chem. 275, 16404-16407), it is plausible that these channels play differential physiological roles in the K+-buffering action of brain astrocytes in a region-specific manner.