Upregulation of Kv1.3 K(+) channels in microglia deactivated by TGF-beta.
Microglial activation is accompanied by changes in K(+) channel expression. Here we demonstrate that a deactivating cytokine changes the electrophysiological properties of microglial cells. Upregulation of delayed rectifier (DR) K(+) channels was observed in microglia after exposure to transforming growth factor-beta (TGF-beta) for 24 h. In contrast, inward rectifier K(+) channel expression was unchanged by TGF-beta. DR current density was more than sixfold larger in TGF-beta-treated microglia than in untreated microglia. DR currents of TGF-beta-treated cells exhibited the following properties: activation at potentials more positive than -40 mV, half-maximal activation at -27 mV, half-maximal inactivation at -38 mV, time dependent and strongly use-dependent inactivation, and a single channel conductance of 13 pS in Ringer solution. DR channels were highly sensitive to charybdotoxin (CTX) and kaliotoxin (KTX), whereas alpha-dendrotoxin had little effect. With RT-PCR, mRNA for Kv1.3 and Kir2.1 was detected in microglia. In accordance with the observed changes in DR current density, the mRNA level for Kv1.3 (assessed by competitive RT-PCR) increased fivefold after treatment of microglia with TGF-beta.
Schilling
T
T
Institut für Physiologie der Charité, Humboldt Universität, D 10117 Berlin, Germany.
Quandt
F N
FN
Cherny
V V
VV
Zhou
W
W
Heinemann
U
U
Decoursey
T E
TE
Eder
C
C
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D004558:Electric Stimulation; D017136:Ion Transport / Q000187:drug effects; D051664:Kv1.3 Potassium Channel; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D051668:Delayed Rectifier Potassium Channels; C496974:Kcna3 protein, mouse; D051664:Kv1.3 Potassium Channel; D009498:Neurotoxins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D011188:Potassium