Hv1 proton channels are required for high-level NADPH oxidase-dependent superoxide production during the phagocyte respiratory burst

Granulocytes generate a "respiratory burst" of NADPH oxidase-dependent superoxide anion (O[Formula: see text]) production that is required for efficient clearance of bacterial pathogens. Hv1 mediates a voltage-gated H⁺ channel activity that is proposed to serve a charge-balancing role in granulocytic phagocytes such as neutrophils and eosinophils. Using mice in which the gene encoding Hv1 is replaced by β-Geo reporter protein sequence, we show that Hv1 expression is required for measurable voltage-gated H⁺ current in unstimulated phagocytes. O[Formula: see text] production is substantially reduced in the absence of Hv1, suggesting that Hv1 contributes a majority of the charge compensation required for optimal NADPH oxidase activity. Despite significant reduction in superoxide production, Hv1⁻/⁻ mice are able to clear several types of bacterial infections.