Interferon-γ acutely induces calcium influx in human microglia

The acute actions of the cytokine, interferon-gamma (IFN-gamma), on intracellular calcium [Ca2+](i) levels in human microglia were investigated. In the presence of a calcium-containing physiological solution (Ca2+-PSS), IFN-gamma caused a progressive increase in [Ca2+](i) to a plateau level with a mean rate of increase of 0.81 +/- 0.17 nM/s and mean amplitude of 102 +/-12 nM (n=67 cells). Washout of the cytokine did not alter the plateau established with IFN-gamma in Ca2+-PSS; however, introduction of a Ca2+-free PSS diminished [Ca2+](i) to baseline levels. The decrease in [Ca2+](i) with Ca2+-free PSS would indicate that the response to IFN-gamma was mediated by an influx pathway. This result was confirmed in separate experiments showing the lack of an induced change in [Ca2+](1) with IFN-gamma applied in Ca2+-free PSS. The increase in [Ca2+](i) inducedin Ca2+-PSS was reduced to near baseline levels when the external solution contained low CI- in the maintained presence of IFN-gamma suggesting that cellular depolarization inhibited the cytokine mediated entry pathway. The compound SKF96365, which blocks store operated influx of Ca2+ in human microglia, was ineffective in altering the increase in [Ca2+](i) however, La3+ completely inhibited the Ca2+ response induced by IFN-gamma. Whole-cell patch clamp studies showed no effect of IFN-gamma to alter outward currents and inward rectifier K+ currents. The influx of Ca2+ may serve a signaling role in microglia linking IFN-gamma to functional responses of the cells to infiltrating T lymphocytes into the central nervous system (CNS) during inflammatory processes. (C) 2002 Wiley-Liss, Inc.