NADPH oxidase is an O2 sensor in airway chemoreceptors: Evidence from K+ current modulation in wild-type and oxidase-deficient mice
AUTOR(ES)
Fu, Xiao Wen
FONTE
The National Academy of Sciences
RESUMO
Pulmonary neuroepithelial bodies (NEBs) are presumed airway chemoreceptors that express the putative O2 sensor protein NADPH oxidase and O2-sensitive K+ channels K+(O2). Although there is a consensus that redox modulation of K+(O2) may be a common O2-sensing mechanism, the identity of the O2 sensor and related coupling pathways are still controversial. To test whether NADPH oxidase is the O2 sensor in NEB cells, we performed patch-clamp experiments on intact NEBs identified by neutral red staining in fresh lung slices from wild-type (WT) and oxidase-deficient (OD) mice. In OD mice, cytochrome b558 and oxidase function was disrupted in the gp91phox subunit coding region by insertion of a neomycin phosphotransferase (neo) gene. Expression in NEB cells of neo mRNA, a marker for nonfunctional gp91phox, was confirmed by nonisotopic in situ hybridization. In WT cells, hypoxia (pO2 = 15–20 mmHg; 1 mmHg = 133 Pa) caused a reversible inhibition (≈46%) of both Ca2+-independent and Ca2+-dependent K+ currents. In contrast, hypoxia had no effect on K+ current in OD cells, even though both K+ current components were expressed. Diphenylene iodonium (1 μM), an inhibitor of the oxidase, reduced K+ current by ≈30% in WT cells but had no effect in OD cells. Hydrogen peroxide (H2O2; 0.25 mM), a reactive oxygen species generated by functional NADPH oxidase, augmented K+ current by >30% in both WT and OD cells; further, in WT cells, H2O2 restored K+ current amplitude in the presence of diphenylene iodonium. We conclude that NADPH oxidase acts as the O2 sensor in pulmonary airway chemoreceptors.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=18249Documentos Relacionados
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