Calcium/calmodulin‐dependent protein kinase II modulates inositol‐3‐phosphate receptors in vascular endothelium from mouse mesenteric arteries (1075.1)
Bibliographic record
Abstract
Endothelial Ca 2+ pulsar consists in a spontaneous Ca 2+ release from IP 3 R localized within myoendothelial projections (MEP). We recently showed CaMKII activation by Ca 2+ pulsars, thus modulating endothelial function through NO production. Moreover, CaMKII is a known regulator of intracellular Ca 2+ homeostasis in several cell types. Our hypothesis was that Ca 2+ pulsar‐activated CaMKII modulates endothelial intracellular Ca 2+ dynamics. Our investigation showed that preincubation with KN‐93 (10 µM), CaMKII inhibitor, significantly altered endoplasmic reticulum (ER) Ca 2+ content (≍ ‐60%). A similar KN‐93‐induced alteration of ER Ca 2+ levels (≍ ‐55%) was observed while SERCA pumps were inhibited (Thapsigargin; 1 µM). However, inhibition of IP 3 R (2APB; 100 µM) precluded KN‐93 effect on ER Ca 2+ content. Colocalization (<40nm) of CaMKII and IP 3 R was observed by PLA in situ hybridization. In addition, an isoform‐specific distribution within MEP (IP 3 R2>IP 3 R1>IP 3 R3) has been found by in situ immunofluorescence. Finally, KN‐93 induced recruitment of new Ca 2+ pulsars sites (1.8‐Fold). These results suggest that CaMKII modulates intracellular Ca 2+ dynamics through modulation of IP 3 R activity. Thereby, CaMKII is involved in a negative feedback loop as an endothelial calcium‐sensor switch regulating Ca 2+ homeostasis. Grant Funding Source : Supported by FRQS, FICM, CFI, SQHA and HSFC
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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 teacher head, 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".