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

Abstract

Whole-cell patch-clamp measurements were performed to investigate voltage-gated proton currents (I PR) in cultured murine microglia of distinct morphology and functional state. We studied I PR in ameboid microglia of untreated cultures, in ameboid microglia which had been activated by lipopolysaccharide, and in ramified microglia which had been exposed to astrocyte-conditioned medium. Proton currents of these three microglia populations did not differ regarding their activation threshold or the voltage dependence of steady-state activation. Moreover, pharmacological properties of I PR were similar: proton currents were sensitive to extracellularly applied Zn 2+ or La 3+, and could be abolished by each of those at a concentration of 100 μM. 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 populations. In contrast, proton currents of microglia differed between the three cell 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 either lipopolysaccharide or astrocyte-conditioned medium. Moreover, I PR activated 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 three microglial populations do not correlate with the functional state of the cells.