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

• Published in: Molecular and cellular neuroscience 2006-12, Vol.33 (4), p.401-411
• Main Authors: Pannasch, Ulrike, Färber, Katrin, Nolte, Christiane, Blonski, Mary, Yan Chiu, Shing, Messing, Albee, Kettenmann, Helmut
• Format: Article
• Language: English
• Subjects: Animals; Brain - cytology; Bromodeoxyuridine - metabolism; Cell Proliferation - drug effects; Cells, Cultured; Chemokines - metabolism; Cytokines - metabolism; Dose-Response Relationship, Radiation; Electric Stimulation - methods; Embryo, Mammalian; Facial Nerve Diseases - metabolism; Facial Nerve Diseases - pathology; Immunohistochemistry - methods; Kv1.3 Potassium Channel - chemistry; Kv1.3 Potassium Channel - physiology; Kv1.5 Potassium Channel - chemistry; Kv1.5 Potassium Channel - genetics; Kv1.5 Potassium Channel - physiology; Lipopolysaccharides - pharmacology; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia - drug effects; Microglia - physiology; Nitric Oxide - metabolism; Oligodeoxyribonucleotides, Antisense - pharmacology; Patch-Clamp Techniques - methods; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2006.08.009

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.