A Kv1.5 to Kv1.3 switch in endogenous hippocampal microglia and a role in proliferation

The proliferation of microglia is a normal process in CNS development and i n the defense against pathological insults, although, paradoxically, it con tributes to several brain diseases. We have examined the types of voltage-a ctivated K+ currents (Kv) and their roles in microglial proliferation. Micr oglia were tissue-printed directly from the hippocampal region using brain slices from 5- to 14-d-old rats. Immediately after tissue prints were prepa red, unipolar and bipolar microglia expressed a large Kv current, and the c ells were not proliferating. Surprisingly, this current was biophysically a nd pharmacologically distinct from Kv1.3, which has been found in dissociat ed, cultured microglia, but it was very similar to Kv1.5. After several day s in culture the microglia became highly proliferative, and although the Kv prevalence and current density decreased, many cells exhibited a prominent Kv that was indistinguishable from Kv1.3. The Kv1.5-like current was prese nt in nonproliferating cells, whereas proliferating cells expressed the Kv1 .3-like current. Immunocytochemical staining showed a dramatic shift in exp ression and localization of Kv1.3 and Kv1.5 proteins in microglia: Kv1.5 mo ving away from the surface and Kv1.3 moving to the surface as the cells wer e cultured. K+ channel blockers inhibited proliferation, and the pharmacolo gy of this inhibition correlated with the type of Kv current expressed. Our study, which introduces a method for the physiological examination of micr oglia from identified brain regions, demonstrates the differential expressi on of two functional Kv subunits and shows that a functional delayed rectif ier current is necessary for microglia proliferation.