During the respiratory burst, do phagocytes need proton channels or potassium channels, or both?

The NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase enzyme complex, a crucial component of innate immunity, produces superoxide anion (O2-), which is a precursor to many reactive oxygen species. NADPH oxidase produces O2- by transferring electrons from intracellular NADPH across the membrane to extracellular (or phagosomal) oxygen and is thus electrogenic. It is widely believed that electroneutrality is preserved by proton flux through voltage-gated proton channels. A series of recent papers have challenged several key aspects of this view of the "respiratory burst." The most recent study solidifies the proposal that O2- and other reactive oxygen species produced by phagocytes are not toxic to microbes under physiological conditions. Further, an essential role for high-conductance, Ca2+-activated K+ (maxi-K+) channels in microbe killing is proposed. Finally, the results cast doubt on the widely held view that H+ efflux through voltage-gated proton channels (i) is the main mechanism of charge compensation, and (ii) is essential to continuous O2- production by the NADPH oxidase. My analysis of the new data and of a large body of data in the literature indicates that the proposed role of maxi-K+ channels in the respiratory burst is not yet credibly established. H+ efflux through proton channels thus remains the most viable mechanism for charge compensation and continuous O2- production. The important question of the toxicity of reactive oxygen species in phagocytes and in other cells, which has long been simply taken for granted, is a widespread assumption that deserves critical study.