During the Respiratory Burst, Do Phagocytes Need Proton Channels or Potassium Channels, or Both?

See allHide authors and affiliations

Science's STKE  18 May 2004:
Vol. 2004, Issue 233, pp. pe21
DOI: 10.1126/stke.2332004pe21

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution


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.

View Full Text

Stay Connected to Science Signaling

Editor's Blog