Pannasch Ulrike, Färber Katrin, Nolte Christiane, Blonski Mary, Yan Chiu Shing, Messing Albee, Kettenmann Helmut
Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Mol Cell Neurosci. 2006 Dec;33(4):401-11. doi: 10.1016/j.mcn.2006.08.009. Epub 2006 Oct 19.
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 Kv1.5(-/-) 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 Kv1.5(-/-) 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.
脂多糖（LPS）激活小胶质细胞会导致细胞因子的诱导释放和一氧化氮（NO）释放，细胞增殖减少，外向钾离子（K(+)）电导增加，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，即Kv1.5基因敲除（Kv1.5(-/-)）小鼠和反义寡核苷酸（AO）方法，研究了这些通道在小胶质细胞功能中的作用。AO Kv1.5可降低LPS诱导的NO释放，而在Kv1.5(-/-)动物中则完全没有NO释放；AO Kv1.3则没有效果。相反，Kv1.3或Kv1.5通道表达缺失均会增加细胞增殖。面神经损伤后，与野生型相比，Kv1.5(-/-)动物的增殖率更高。膜片钳实验证实，在Kv1.5(-/-)小胶质细胞以及经Kv1.5或Kv1.3 AO处理的细胞中，LPS诱导的外向电流幅度降低。我们的研究表明，K(+)通道表达的诱导是小胶质细胞激活的完整功能谱的先决条件。
