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少突胶质细胞和祖细胞中延迟整流钾通道的特性分析。

Characterization of delayed rectifier Kv channels in oligodendrocytes and progenitor cells.

作者信息

Attali B, Wang N, Kolot A, Sobko A, Cherepanov V, Soliven B

机构信息

Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.

出版信息

J Neurosci. 1997 Nov 1;17(21):8234-45. doi: 10.1523/JNEUROSCI.17-21-08234.1997.

Abstract

We examined the molecular identity of K+ channel genes underlying the delayed rectifier (IK) in differentiated cultured oligodendrocytes (OLGs) and oligodendrocyte progenitor (OP) cells. Using reverse transcription-PCR cloning, we found that OP cells and OLGs expressed multiple Kv transcripts, namely Kv1.2, Kv1.4, Kv.1.5, and Kv1.6. Immunocytochemical and Western blot analyses revealed that Kv1.5 and Kv1.6 as well as Kv1.2 and Kv1.4 channel proteins could be detected in these cells, but definitive evidence for functional K+ channel expression was obtained only for the Kv1.5 channel. In addition, mRNA and immunoreactive protein levels of both Kv1.5 and Kv1.6 channels were significantly lower in differentiated OLGs when compared with levels in OP cells. Proliferation of OP cells was inhibited by K+ channel blockers, but not by incubation with either Kv1.5 or Kv1.6 antisense oligonucleotides. We conclude that (1) IK in OP cells and OLGs is encoded partly by Kv1.5 subunits, possibly forming heteromultimeric channels with Kv1.6 or other Kv subunits; and (2) inhibition of Kv1.5 or Kv1.6 channel expression alone does not prevent mitogenesis. Concomitant inhibition of other Kv channels underlying IK may be necessary for OP cells to exit from cell cycle.

摘要

我们研究了分化的培养少突胶质细胞(OLGs)和少突胶质前体细胞(OP)中延迟整流钾通道(IK)相关钾通道基因的分子特性。通过逆转录 - PCR克隆,我们发现OP细胞和OLGs表达多种Kv转录本,即Kv1.2、Kv1.4、Kv1.5和Kv1.6。免疫细胞化学和蛋白质印迹分析表明,在这些细胞中可检测到Kv1.5和Kv1.6以及Kv1.2和Kv1.4通道蛋白,但仅获得了Kv1.5通道功能性钾通道表达的确切证据。此外,与OP细胞中的水平相比,分化的OLGs中Kv1.5和Kv1.6通道的mRNA和免疫反应性蛋白水平均显著降低。OP细胞的增殖受到钾通道阻滞剂的抑制,但与Kv1.5或Kv1.6反义寡核苷酸孵育则无此作用。我们得出结论:(1)OP细胞和OLGs中的IK部分由Kv1.5亚基编码,可能与Kv1.6或其他Kv亚基形成异源多聚体通道;(2)单独抑制Kv1.5或Kv1.6通道表达并不能阻止有丝分裂。对于OP细胞退出细胞周期,可能需要同时抑制IK相关的其他Kv通道。

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