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The voltage dependence of NADPH oxidase reveals why phagocytes need proton channels

Author

Listed:
  • Thomas E. DeCoursey

    (Rush Presbyterian St Luke's Medical Center)

  • Deri Morgan

    (Rush Presbyterian St Luke's Medical Center)

  • Vladimir V. Cherny

    (Rush Presbyterian St Luke's Medical Center)

Abstract

The enzyme NADPH oxidase in phagocytes is important in the body's defence against microbes: it produces superoxide anions (O2-, precursors to bactericidal reactive oxygen species1). Electrons move from intracellular NADPH, across a chain comprising FAD (flavin adenine dinucleotide) and two haems, to reduce extracellular O2 to O2-. NADPH oxidase is electrogenic2, generating electron current (Ie) that is measurable under voltage-clamp conditions3,4. Here we report the complete current–voltage relationship of NADPH oxidase, the first such measurement of a plasma membrane electron transporter. We find that Ie is voltage-independent from -100 mV to >0 mV, but is steeply inhibited by further depolarization, and is abolished at about +190 mV. It was proposed that H+ efflux2 mediated by voltage-gated proton channels5,6 compensates Ie, because Zn2+ and Cd2+ inhibit both H+ currents7,8,9 and O2- production10. Here we show that COS-7 cells transfected with four NADPH oxidase components11, but lacking H+ channels12, produce O2- in the presence of Zn2+ concentrations that inhibit O2- production in neutrophils and eosinophils. Zn2+ does not inhibit NADPH oxidase directly, but through effects on H+ channels. H+ channels optimize NADPH oxidase function by preventing membrane depolarization to inhibitory voltages.

Suggested Citation

  • Thomas E. DeCoursey & Deri Morgan & Vladimir V. Cherny, 2003. "The voltage dependence of NADPH oxidase reveals why phagocytes need proton channels," Nature, Nature, vol. 422(6931), pages 531-534, April.
  • Handle: RePEc:nat:nature:v:422:y:2003:i:6931:d:10.1038_nature01523
    DOI: 10.1038/nature01523
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    Cited by:

    1. Chang Zhao & Parker D. Webster & Alexis Angeli & Francesco Tombola, 2023. "Mechanically-primed voltage-gated proton channels from angiosperm plants," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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