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

Thomas E. DeCoursey (), Deri Morgan and Vladimir V. Cherny
Additional contact information
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

Nature, 2003, vol. 422, issue 6931, 531-534

Abstract: 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.

Date: 2003
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature01523 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:422:y:2003:i:6931:d:10.1038_nature01523

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01523

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().