Figure 1. Functional roles of voltage-gated proton channels of immune cells.

Both neutrophils and B lymphocytes possess a superoxide-generating enzyme, the NADPH oxidase that assembles at the plasma membrane upon phosphorylation. A, neutrophils produce high levels of superoxide radicals (O₂⁻) that help kill bacteria. The large flux of electrons across the oxidase (yellow) depolarises the plasma membrane, whereas the protons released by the oxidation and regeneration of NADPH acidify the cytosol, two conditions that, together with phosphorylation, activate voltage-gated proton channels (blue). Proton channels extrude the cytosolic acid, repolarise the plasma membrane, and deliver extracellular protons used to convert superoxide to hydrogen peroxide (H₂O₂). Acid extrusion and membrane repolarisation sustain the activity of the oxidase and enhance the entry of calcium across membrane channels to boost cell signalling. B, in activated B lymphocytes, VSOP/Hv1channels also sustain the production of superoxide, but the H₂O₂ generated diffuses inside cells to oxidise and inactivate the tyrosine phosphatase SHP-1, promoting the phosphorylation of the antigen-bound B cell antigen receptor to boost cell signalling.