The potassium channels Kv1.5 and Kv1.3 modulate distinct functions of microglia
The potassium channels Kv1.5 and Kv1.3 modulate distinct functions of microglia
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DOI：
10.1016/j.mcn.2006.08.009
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发表时间：
2006-12-01
影响因子：
3.5
通讯作者：
Kettenmann, Helmut
中科院分区：
文献类型：
--
作者：
Pannasch, Ulrike;Faerber, Katrin;Kettenmann, Helmut
内毒素激活小胶质细胞可诱导细胞因子和NO释放，抑制细胞增殖，增加外向K+电导，后者涉及Kv1.5和Kv1.3通道的激活。我们使用两种干扰通道表达的策略来研究这些通道对小胶质细胞功能的作用，Kv1.5基因敲除(Kv1.5(-/-))小鼠和反义寡核苷酸(AO)方法。AOKv1.5可减少内毒素诱导的NO释放，而Kv1.51(-/-)动物则完全消失，而AOKv1.3则无此作用。相反，Kv1.3或Kv1.5通道表达缺失均可促进细胞增殖。面神经损伤后，Kv1.51(-/-)动物的增殖率高于野生型。膜片钳实验证实，Kv1.5(-/-)小胶质细胞以及经Kv1.5或Kv1.3 AO处理的小胶质细胞的内毒素诱导的外向电流幅度降低。我们的研究表明，诱导K+通道的表达是小胶质细胞激活的完整功能谱的先决条件。(C)2006 Elsevier Inc.保留所有权利。
Activation of microglia by LPS leads to an induction of cytokine and NO release, reduced proliferation and increased outward K+ conductance, the latter involving the activation of Kv1.5 and Kv1.3 channels. We studied the role of these channels for microglial function using two strategies to interfere with channel expression, a Kv1.5 knockout (Kv1.5(-/-)) mouse and an antisense oligonucleotide (AO) approach. The LPS-induced NO release was reduced by AO Kv1.5 and completely absent in the Kv1.51(-/-) animal; the AO Kv1.3 had no effect. In contrast, proliferation was augmented with both, loss of Kv1.3 or Kv1.5 channel expression. After facial nerve lesion, proliferation rate was higher in Kv1.51(-/-) animals as compared to wild type. Patch clamp experiments confirmed the reduction of the LPS-induced outward current amplitude in Kv1.5(-/-) microglia as well as in Kv1.5- or Kv1.3 AO-treated cells. Our study indicates that induction of K+ channel expression is a prerequisite for the full functional spectrum of microglial activation. (c) 2006 Elsevier Inc. All rights reserved.