Upregulation of Kv1.3 K+ channels in microglia deactivated by TGF-beta

Microglial activation is accompanied by changes in K+ channel expression. H ere we demonstrate that a deactivating cytokine changes the electrophysiolo gical properties of microglial cells. Upregulation of delayed rectifier (DR ) K+ channels was observed in microglia after exposure to transforming grow th factor-beta (TGF-beta) for 24 h. In contrast, inward rectifier K+ channe l expression was unchanged by TGF-beta. DR current density was more than si xfold larger in TGF-beta-treated microglia than in untreated microglia. DR currents of TGF-beta-treated cells exhibited the following properties: acti vation at potentials more positive than -40 mV, half-maximal activation at -27 mV, half-maximal inactivation at -38 mV, time dependent and strongly us e-dependent inactivation, and a single channel conductance of 13 pS in Ring er solution. DR channels were highly sensitive to charybdotoxin (CTX) and k aliotoxin (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 wit h TGF-beta.