Voltage-gated proton currents in microglia of distinct morphology and functional state

Whole-cell patch-clamp measurements were performed to investigate voltage-g ated proton currents (I-PR) in cultured murine microglia of distinct morpho logy and functional state. We studied I-PR in ameboid microglia of untreate d cultures, in ameboid microglia which had been activated by lipopolysaccha ride, and in ramified microglia which had been exposed to astrocyte-conditi oned medium. Proton currents of these three microglia populations did not d iffer regarding their activation threshold or the voltage dependence of ste ady state activation. Moreover, pharmacological properties of I-PR were sim ilar: proton currents were sensitive to extracellularly applied Zn2+ or La3 +, and could be abolished by each of those at a concentration of 100 mu M. In the presence of extracellular Na+, I-PR was decreased to a similar small extent due to activity of the Na+/H+ exchanger in all microglial populatio ns. In contrast, proton currents of microglia differed between the three ce ll populations with respect to their current density and their time-course of activation: in comparison with untreated microglia, the current density of I-PR was reduced by about 50% in microglia after their treatment with ei ther lipopolysaccharide or astrocyte-conditioned medium. Moreover, I-PR act ivated significantly more slowly in cells exposed to lipopolysaccharide or astrocyte-conditioned medium than in untreated cells. It can be concluded that the distinct H+ current characteristics of the thr ee microglial populations do not correlate with the functional state of the cells. (C) 1999 IBRO. Published by Elsevier Science Ltd.