Expression of Kir4.1 and Kir5.1 inwardly rectifying potassium channels in oligodendrocytes, the myelinating cells of the CNS.
Expression of Kir4.1 and Kir5.1 inwardly rectifying potassium channels in oligodendrocytes, the myelinating cells of the CNS.
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DOI：
10.1007/s00429-016-1199-8
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发表时间：
2017-01
影响因子：
3.1
通讯作者：
Butt AM
中科院分区：
文献类型：
--
作者：
Brasko C;Hawkins V;De La Rocha IC;Butt AM
内向整流K+通道亚型Kir5.1仅作为Kir4.1的异构体通道起作用。在中枢神经系统中，Kir4.1定位于星形胶质细胞，是星形胶质细胞膜电位强负的分子基础。少突胶质细胞是中枢神经系统中特殊的髓鞘胶质细胞，它们的静息膜电位为髓鞘形成所必需的离子和水运输提供了动力。然而，对成熟的髓鞘少突胶质细胞的离子通道分布知之甚少。在这里，我们首次鉴定了Kir5.1和Kir4.1在白质少突胶质细胞中的共存。用膜结合的Na+/K+-ATPase和免疫印迹法对视神经的质膜部分进行免疫定位，发现Kir4.1和Kir5.1共同定位于少突胶质细胞膜上。免疫共沉淀证明少突胶质细胞和星形胶质细胞表达同源Kir4.1和异构体Kir4.1/Kir5.1通道。基因敲除和shRNA去除Kir4.1表明，Kir5.1在胶质细胞中的表达在很大程度上依赖于Kir4.1和质膜锚定蛋白PSD-95。结果表明，除星形胶质细胞外，少突胶质细胞还表达同质性Kir4.1和异构性Kir4.1/Kir5.1通道。在星形胶质细胞中，这些通道对其吸收K+和CO2/H+化学感受的关键功能是必不可少的。我们认为Kir4.1/Kir5.1通道在少突胶质细胞中具有同等的功能，在动作电位沿有髓轴突传播的大离子位移面前保持髓鞘完整性。
The inwardly rectifying K+ channel subtype Kir5.1 is only functional as a heteromeric channel with Kir4.1. In the CNS, Kir4.1 is localised to astrocytes and is the molecular basis of their strongly negative membrane potential. Oligodendrocytes are the specialised myelinating glia of the CNS and their resting membrane potential provides the driving force for ion and water transport that is essential for myelination. However, little is known about the ion channel profile of mature myelinating oligodendrocytes. Here, we identify for the first time colocalization of Kir5.1 with Kir4.1 in oligodendrocytes in white matter. Immunolocalization with membrane-bound Na+/K+-ATPase and western blot of the plasma membrane fraction of the optic nerve, a typical CNS white matter tract containing axons and the oligodendrocytes that myelinate them, demonstrates that Kir4.1 and Kir5.1 are colocalized on oligodendrocyte cell membranes. Co-immunoprecipitation provides evidence that oligodendrocytes and astrocytes express a combination of homomeric Kir4.1 and heteromeric Kir4.1/Kir5.1 channels. Genetic knock-out and shRNA to ablate Kir4.1 indicates plasmalemmal expression of Kir5.1 in glia is largely dependent on Kir4.1 and the plasmalemmal anchoring protein PSD-95. The results demonstrate that, in addition to astrocytes, oligodendrocytes express both homomeric Kir4.1 and heteromeric Kir4.1/Kir5.1 channels. In astrocytes, these channels are essential to their key functions of K+ uptake and CO2/H+ chemosensation. We propose Kir4.1/Kir5.1 channels have equivalent functions in oligodendrocytes, maintaining myelin integrity in the face of large ionic shifts associated with action potential propagation along myelinated axons.