The potassium channels Kv1.5 and Kv1.3 modulate distinct functions of microglia

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.