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.