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PMID: 11559775 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Activation of NADPH oxidase-related proton and electron currents in human eosinophils by arachidonic acid.

The Journal of physiology ·Vol. 535 ·No. Pt 3 ·2001-09-15 ·Pages 783-94

Cherny VV, Henderson LM, Xu W, Thomas LL, DeCoursey TE

Abstract

1. Effects of arachidonic acid (AA) on proton and electron currents in human eosinophils were studied using the permeabilized-patch voltage-clamp technique, using an applied NH4+ gradient to control pH(i). 2. Superoxide anion (O2-) release was assessed by cytochrome c reduction in human eosinophils. Significant O2- release was stimulated by 5-10 microM AA. 3. AA activated diphenylene iodinium (DPI)-inhibitable inward current reflecting electron efflux through NADPH oxidase. These electron currents (I(e)) were elicited in human eosinophils at AA concentrations (3-10 microM) similar to those that induced O2- release. 4. The voltage-gated proton conductance (g(H)) in eosinophils stimulated with AA was profoundly enhanced: H+ current amplitude (I(H)) increased 4.6 times, activation was 4 times faster, and the H+ conductance-voltage (g(H)-V) relationship was shifted to substantially more negative voltages. The electrophysiological effects of AA resembled those reported for PMA, except that AA did not consistently slow tau(tail) (deactivation of H+ currents). 5. The stimulation of both proton and electron currents by AA was reversible upon washout. Repeated exposure elicited repeated responses. The activation of H+ currents by AA was dissociable from its activation of NADPH oxidase; H+ currents were enhanced at low concentrations of AA that did not elicit detectable I(e) or when NADPH oxidase was inhibited by DPI. 6. Most of the effects of AA on H+ currents qualitatively resemble those reported in whole-cell studies, reflecting a more direct action than PMA. The results are compatible with AA being an immediate activator of both NADPH oxidase and proton channels in human eosinophils.

MeSH Terms
Arachidonic Acid/pharmacology Dose-Response Relationship, Drug Electrons Eosinophils/drug effects,metabolism Humans In Vitro Techniques Ion Channel Gating/drug effects Ion Channels/agonists NADPH Oxidases/physiology Oxygen Consumption/drug effects Protons Stimulation, Chemical
Chemicals
Ion Channels Protons Arachidonic Acid NADPH Oxidases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cherny V V
Department of Molecular Biophysics and Physiology, Rush Presbyterian St Luke's Medical Center, Chicago, IL 60612, USA. tdecours@rush.edu
Henderson L M
Xu W
Thomas L L
DeCoursey T E
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1111/j.1469-7793.2001.00783.x
Email
tdecours@rush.edu
Published
2001-09-15
Pages
783-94
Language
English
Region
England
NLM ID
0266262
PMCID
PMC2278825
Subset
IM
Grants
NHLBI NIH HHS · R01 HL052671 · United States
NHLBI NIH HHS · R01 HL061437 · United States
NIAID NIH HHS · AI48160 · United States
NHLBI NIH HHS · HL52671 · United States
NHLBI NIH HHS · HL61437 · United States
External Links
PubMed source DOI: 10.1111/j.1469-7793.2001.00783.x PMC Full Text View journal details
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