Mechanosensitivity of Murine Lung Slowly Adapting Receptors: Minimal Impact of Chemosensory, Serotonergic, and Purinergic Signaling
Bibliographic record
Abstract
Murine slowly adapting receptors (SARs) within airway smooth muscle provide volume-related feedback; however, their mechanosensitivity and morphology are incompletely characterized. We explored two aspects of SAR physiology: their inherent static mechanosensitivity and a potential link to pulmonary neuroepithelial bodies (NEBs). SAR mechanosensitivity displays a rate sensitivity linked to speed of inflation; however, to what extent static SAR mechanosensitivity is tuned for the very rapid breathing frequency (Bf) of small mammals (e.g., mouse) is unclear. NEB-associated, morphologically described smooth muscle-associated receptors (SMARs) may be a structural analog for functionally characterized SARs, suggesting functional linkages between SARs and NEBs. We addressed the hypotheses that: (1) rapid murine Bf is associated with enhanced in vivo SAR static sensitivity; (2) if SARs and NEBs are functionally linked, stimuli reported to impact NEB function would alter SAR mechanosensitivity. We measured SAR action potential discharge frequency (AP f, action potentials/s) during quasi-static inflation [0–20 cmH2O trans-respiratory pressure (PTR)] in NEB-relevant conditions of hypoxia (FIO2 = 0.1), hypercarbia (FICO2 = 0.1), and pharmacologic intervention (serotonergic 5-HT3 receptor antagonist, Tropisetron, 4.5 mg/kg; P2 purinergic receptor antagonist, Suramin, 50 mg/kg). In all protocols, we obtained: (1) AP f vs. PTR; (2) PTR threshold; and (3) AP f onset at PTR threshold. The murine AP f vs. PTR response comprises high AP f (average maximum AP f: 236.1 ± 11.1 AP/s at 20 cmH2O), a low PTR threshold (mean 2.0 ± 0.1 cmH2O), and a plateau in AP f between 15 and 20 cmH2O. Murine SAR mechanosensitivity (AP f vs. PTR) is up to 60% greater than that reported for larger mammals. Even the maximum difference between intervention and control conditions was minimally impacted by NEB-related alterations: Tropisetron −7.6 ± 1.8% (p = 0.005); Suramin −10.6 ± 1.5% (p = 0.01); hypoxia +9.3 ± 1.9% (p < 0.001); and hypercarbia −6.2 ± 0.9% (p < 0.001). We conclude that the high sensitivity of murine SARs to inflation provides enhanced resolution of operating lung volume, which is aligned with the rapid Bf of the mouse. We found minimal evidence supporting a functional link between SARs and NEBs and speculate that the <10% change in SAR mechanosensitivity during altered NEB-related stimuli is not consistent with a meaningful physiologic role.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".