Signaling pathways underlying the P2Y <sub>1</sub> receptor‐mediated excitation of the preBötzinger Complex (preBötC) inspiratory rhythm generating network in vitro
Bibliographic record
Abstract
The ventilatory response to hypoxia comprises an initial increase in ventilation followed by a secondary depression. The release of ATP within the respiratory network, including the preBötC, attenuates the depression, in part via a P2Y 1 receptor (R), preBötC mechanism involving neurons and glia. To characterize the signaling pathways underlying the P2Y 1 excitation, we used primary cultures of preBötC astrocytes loaded with Fluo‐4 and compared the fluorescence response evoked by ATP (10 μM) in control and after bath application of carbenoxolone (CBX, gap junction blocker 100 μM) and membrane permeant 2 nd messenger blockers. CBX had no effect but U73122 (phospholipase C antagonist) and thapsigargin (depletes intracellular Ca 2+ (Ca 2+ i ) stores) blocked ATP‐evoked Ca 2+ i increases. In rhythmic medullary slices from neonatal rat, CBX had no effect on the frequency (f) response evoked by ATP (100 μM, 10 sec) in the preBötC. To test the role of Ca 2+ i we compared the f response to MRS2365 (P2Y 1 R agonist, 100 μM) before and after application of EGTA‐AM (1 mM) into the preBötC. EGTA reduced the control, 2.2±0.3 fold MRS2365 f increase by 64±7%. Response duration fell to 35±6% of control. In cultured preBötC glia, ATP‐evoked Ca 2+ i increases reflect PLC‐induced release from intracellular stores. In the preBötC, increases in Ca 2+ i contribute to the P2Y 1 ‐evoked frequency increase. Supported by CIHR, WCHRI, AIHS & ALA.
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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".