title: The potassium channels Kv1.5 and Kv1.3 modulate distinct functions of microglia.
abstract: 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.
authors.affiliation: Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pannasch
authors.forename: Katrin
authors.initials: K
authors.lastname: Färber
authors.forename: Christiane
authors.initials: C
authors.lastname: Nolte
authors.forename: Mary
authors.initials: M
authors.lastname: Blonski
authors.forename: Shing
authors.initials: S
authors.lastname: Yan Chiu
authors.forename: Albee
authors.initials: A
authors.lastname: Messing
authors.forename: Helmut
authors.initials: H
authors.lastname: Kettenmann
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D005155:Facial Nerve Diseases / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D051664:Kv1.3 Potassium Channel / Q000737:chemistry / Q000502:physiology*; D051666:Kv1.5 Potassium Channel / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D018925:Chemokines; D016207:Cytokines; D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008070:Lipopolysaccharides; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D009569:Nitric Oxide; D001973:Bromodeoxyuridine