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 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".