NADPH oxidase is an O <sub>2</sub> sensor in airway chemoreceptors: Evidence from K <sup>+</sup> current modulation in wild-type and oxidase-deficient mice
Bibliographic record
Abstract
Pulmonary neuroepithelial bodies (NEBs) are presumed airway chemoreceptors that express the putative O(2) sensor protein NADPH oxidase and O(2)-sensitive K(+) channels K(+)(O(2)). Although there is a consensus that redox modulation of K(+)(O(2)) may be a common O(2)-sensing mechanism, the identity of the O(2) sensor and related coupling pathways are still controversial. To test whether NADPH oxidase is the O(2) 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 b(558) and oxidase function was disrupted in the gp91(phox) subunit coding region by insertion of a neomycin phosphotransferase (neo) gene. Expression in NEB cells of neo mRNA, a marker for nonfunctional gp91(phox), was confirmed by nonisotopic in situ hybridization. In WT cells, hypoxia (pO(2) = 15-20 mmHg; 1 mmHg = 133 Pa) caused a reversible inhibition ( approximately 46%) of both Ca(2+)-independent and Ca(2+)-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 microM), an inhibitor of the oxidase, reduced K(+) current by approximately 30% in WT cells but had no effect in OD cells. Hydrogen peroxide (H(2)O(2); 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, H(2)O(2) restored K(+) current amplitude in the presence of diphenylene iodonium. We conclude that NADPH oxidase acts as the O(2) sensor in pulmonary airway chemoreceptors.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".