Cyclic AMP regulates potassium channel expression in C6 glioma by destabilizing Kv1.1 mRNA
Cyclic AMP regulates potassium channel expression in C6 glioma by destabilizing Kv1.1 mRNA
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DOI：
10.1073/pnas.95.13.7693
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发表时间：
1998-06-23
影响因子：
11.1
通讯作者：
Tempel, BL
中科院分区：
文献类型：
--
作者：
Allen, ML;Koh, DS;Tempel, BL
各种克隆的电压门控性钾通道基因的组织分布和生理特性已被广泛表征，但对控制这些基因表达的机制知之甚少。在这里，我们报告的研究Kv1.1在C6胶质瘤细胞系内源性表达的调节。我们证明，细胞内cAMP的升高导致Kv1.1 RNA的加速降解。cAMP诱导的Kv1.1 RNA减少，随后是Kv1.1蛋白的减少和全细胞持续Kf电流幅度的减少。Kv1.1的相对特异性阻断剂Dendrotoxin-I阻断胶质瘤细胞中96%的持续K+电流，导致静息膜电位从-40 mV移动到-7 mV。这些数据表明Kv1.1的表达有助于设定未分化胶质瘤细胞中的静息膜电位，因此，我们认为，受体介导的cAMP升高降低外向K+电流密度的作用在翻译水平，以不稳定的Kv1.1 RNA，一个额外的机制，调节钾通道基因的表达。
The tissue distributions and physiological properties of a variety of cloned voltage-gated potassium channel genes have been characterized extensively, yet relatively little is known about the mechanisms controlling expression of these genes. Here, we report studies on the regulation of Kv1.1 expressed endogenously in the C6 glioma cell line. We demonstrate that elevation of intracellular cAMP leads to the accelerated degradation of Kv1.1 RNA. The cAMP-induced decrease in Kv1.1 RNA is followed by a decrease in Kv1.1 protein and a decrease in the whole cell sustained Kf current amplitude. Dendrotoxin-I, a relatively specific blocker of Kv1.1 blocks 96% of the sustained K+ current in glioma cells, causing a shift in the resting membrane potential from -40 mV to -7 mV, These data suggest that expression of Kv1.1 contributes to setting the resting membrane potential in undifferentiated glioma cells, We therefore suggest that receptor-mediated elevation of cAMP reduces outward K+ current density by acting at the translational level to destabilize Kv1.1 RNA, an additional mechanism for regulating potassium channel gene expression.