Basal and ACh‐stimulated intracellular Ca <sup>2+</sup> signals in intact endothelium originate from IP <sub>3</sub> ‐sensitive stores
Bibliographic record
Abstract
Intracellular Ca 2+ in the endothelium regulates vascular function. However, endothelial Ca 2+ signaling is highly dynamic. Endothelial Ca 2+ signaling was investigated in intact endothelium of cut‐open mesenteric arteries from mouse, using the Ca 2+ sensitive dye, Fluo‐4, and a laser scanning confocal microscope. Endothelial Ca 2+ events consisted of waves and oscillations that are stimulated by acetylcholine (ACh, 10 μM). Blocking SK and IK channels had no acute effect on basal Ca 2+ signals, although the global Ca 2+ concentration was reduced by 15 ± 5%. In contrast, depletion of intracellular Ca 2+ stores by CPA (30 μM) decreased Ca 2+ event frequency, indicating that Ca 2+ events originate from intracellular Ca 2+ sources. Ryanodine (50 μM) had little, if any, influence on endothelial Ca 2+ events, suggesting that RyRs are not involved in endothelial Ca 2+ signaling. However, inhibition of IP 3 receptors (IP 3 Rs) with Xestospongin C (50 μM) almost completely abolished basal Ca 2+ events and blocked their enhancement by ACh. Similar results were obtain by U‐73122 (10 μM), suggesting that IP 3 ‐mediated calcium release from internal stores generate the endothelial Ca 2+ signals. Therefore, dynamic Ca 2+ signals in mouse endothelium are not directly dependent on membrane potential, and mainly originate from activation of IP 3 Rs. Supported by NIH (HL44455 & HL63722) and CIHR.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".