Interferon‐γ acutely induces calcium influx in human microglia

The acute actions of the cytokine, interferon‐γ (IFN‐γ), on intracellular calcium [Ca 2+ ] i levels in human microglia were investigated. In the presence of a calcium‐containing physiological solution (Ca 2+ ‐PSS), IFN‐γ caused a progressive increase in [Ca 2+ ] 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‐γ in Ca 2+ ‐PSS; however, introduction of a Ca 2+ ‐free PSS diminished [Ca 2+ ] i to baseline levels. The decrease in [Ca 2+ ] i with Ca 2+ ‐free PSS would indicate that the response to IFN‐γ was mediated by an influx pathway. This result was confirmed in separate experiments showing the lack of an induced change in [Ca 2+ ] i with IFN‐γ applied in Ca 2+ ‐free PSS. The increase in [Ca 2+ ] i induced in Ca 2+ ‐PSS was reduced to near baseline levels when the external solution contained low Cl − in the maintained presence of IFN‐γ suggesting that cellular depolarization inhibited the cytokine mediated entry pathway. The compound SKF96365, which blocks store operated influx of Ca 2+ in human microglia, was ineffective in altering the increase in [Ca 2+ ] i , however, La 3+ completely inhibited the Ca 2+ response induced by IFN‐γ. Whole‐cell patch clamp studies showed no effect of IFN‐γ to alter outward currents and inward rectifier K + currents. The influx of Ca 2+ may serve a signaling role in microglia linking IFN‐γ to functional responses of the cells to infiltrating T lymphocytes into the central nervous system (CNS) during inflammatory processes. © 2002 Wiley‐Liss, Inc.