IP3R‐dependent modulation of endothelial Ca2+ dynamics by CaMKII in mouse mesenteric arteries
Bibliographic record
Abstract
Local calcium dynamics such as Ca 2+ pulsars appear to have a significant impact on endothelial function. These Ca 2+ pulsars result from the spontaneous release of Ca 2+ by IP 3 receptors (IP 3 R) localized within the myoendothelial junction (MJ). We have recently shown that CaMKII, a Ca 2+‐ dependent kinase decoding Ca 2+ oscillations, is activated by Ca 2+ pulsars. However, CaMKII also regulates intracellular Ca 2+ homeostasis in other cell types. CaMKII regulation of endothelial intracellular Ca 2+ dynamics in native endothelium was then undertaken by confocal microscopy. Exposure to KN‐93, a CaMKII inhibitor, stimulated Ca 2+ pulsar. In the absence of extracellular Ca 2+ , exposure to ionomycin provoked an increase in intracellular Ca 2+ , indicative of the endoplasmic reticulum (ER) content in Ca 2+ . Interestingly, preincubation with KN‐93 significantly impaired the ER Ca 2+ content (−62%). However, SERCA inhibition by thapsigargin did not significantly alter the ionomycin‐induced Ca 2+ increase in the presence of KN‐93. These results suggest that CaMKII regulates endothelial Ca 2+ through the modulation of IP 3 R activity. Immunohistochemistry revealed a progressive intrusion of the different isoforms (IP 3 R2>;IP 3 R1>;IP 3 R3) within the MJ. Therefore, this study suggests that endothelial CaMKII inhibits Ca 2+ pulsars through IP 3 R1/2 phosphorylation. Supported by FRQS, FICM, CFI 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 | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".