Microglia cells are versatile players coordinating inflammatory and regenerative processes in the central nervous system. We investigated the activation of ion currents and ATP secretion by sphingosine-1-phosphate (S1P) and hypoosmolarity in microglia BV-2 cells. S1P and extracellular hypoosmolar solution evoked an anion conductance with almost linearly time-dependent increasing amplitude. The currents were inhibited by intracellular hypoosmolar solution and by use of the anion channel antagonists NPPB and tamoxifen pointing to the activation of volume-regulated-anion channels (VRAC). The analysis by qPCR indicated the expression of S1P-receptor-subtypes 1, 2, 4 and 5 in the BV-2 cells. The use of the S1PR1-antagonist W123 and the incubation with pertussis-toxin prevented the S1P-currents showing the involvement of the Gi-protein-coupled S1PR1 in the activation of VRAC by S1P. According to the progress in the molecular identification of VRAC-channels, we found a high inhibition of S1P- and hypoosmolariy-induced VRAC-currents after LRRC8A-knockdown whereas knockdown of subtypes B-D did not significantly influence the currents. Subtype E was not present in BV-2 cells as revealed by qPCR. Furthermore, S1P and hypoosmolar buffer induced an increase of ATP-levels in the supernatants of BV-2 cells being sensitive to treatment with NPPB, tamoxifen and W123. This indicates that in microglia cells sphingosine-1-phosphate or hypoosmolarity mediate an ATP-secretion via volume-dependent anion channel LRRC8 proteins.