Mechanistic insight into the suppression of microglial ROS production by voltage-gated proton channels (VSOP/Hv1).

Voltage-gated proton channels (VSOP/Hv1) reportedly promote reactive oxygen species (ROS) production in several immune cell types. However, we recently reported that primary microglia from VSOP/Hv1-deficient mice show higher ROS production than those from WT mice. Microglia may show a distinct activation status between WT and VSOP/Hv1-deficient cells, leading to a distinct level of ROS production between them. This is unlikely, however, because ROS production in VSOP/Hv1-deficient microglia remained higher than in WT microglia when the cells were exposed to LPS. Further, this increase in ROS production in VSOP/Hv1-deficient cells was not observed in macrophages, which suggests microglia have a unique mechanism of VSOP/Hv1-dependent ROS regulation. The mechanism underlying this unconventional ROS regulation by VSOP/Hv1 in microglia is discussed.