Loss of the calcium-sensing receptor (CaSR) decreases slowly-adapting receptor responsiveness to mechanical stretch independent of oxygenation status
Bibliographic record
Abstract
The CaSR plays an integral role in the regulation of parathyroid hormone (Pth) and is widely expressed in the epithelium of the developing lung ( J Physiol 586:2008). Recently, Lambrecht et al. reported CaSR is expressed on the cells of neuroepithelial bodies (NEB) in the post-natal lung (J Cell Sci 126:2013). NEB are proposed to act as both hypoxia sensors and mechanosensors; however, while in vitro and morphological evidence supports both roles, neither hypothesis has been functionally addressed in vivo . We employed a double-knockout (CaSR -/- , Pth -/- ; KO) mouse model to examine the impact of loss of CaSR on pulmonary mechano- and chemo- sensation, as assessed via action potential discharge in single, vagal, slowly-adapting receptors (SAR) during quasi-static inflation in hyperoxic (40% O 2 -, 60% N 2 ) and hypoxic (10% O 2 , 90%N 2 ) conditions. Hypoxia did not alter the discharge frequency ( f ) vs tracheal pressure (Ptr) relationship in wildtype (WT; n = 7) or CaSR- KO (n= 7) mice (P > 0.05). In normoxia, KO mice exhibited decreased f compared with WT mice (P = 0.001, 2-way ANOVA; mean + SEM: Ptr=5cmH 2 O: WT, 86+9.3 vs KO, 74+7.1; 10cmH 2 O: 148+10.7 vs 111+8.2; 15cmH 2 O: 191+18.8 vs 124+9.1; 20cmH 2 O:150+40.7 vs 116+8.6). During hypoxia, KO mice showed a similarly reduced f vs Ptr relationship vs the WT (P<0.001). We conclude that hypoxia does not alter murine SAR mechanosensitivity whereas, loss of CaSR function reduces SAR mechanosensitivity. We identify a novel mechanism involved in SAR mechanosensitivity to lung inflation relevant to the physiology of pulmonary sensation and respiratory phenotypes of individuals exhibiting CaSR mutations.
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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 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".