Endothelial Mitochondria Regulate Local Calcium Signalling in Mesenteric Arteries From Mice
Bibliographic record
Abstract
Local calcium (Ca 2+ ) signals are crucial for endothelial functions, including regulation of underlying smooth muscle cell contractility. Ca 2+ pulsar is an endothelial IP 3 R‐dependent Ca 2+ signal restricted to myoendothelial projections (MEP). Targets for this spatially‐discrete Ca 2+ signal such as K Ca 3.1 channels, NOS3 and CaMKII have been previously described. However, determinants for Ca 2+ pulsar kinetics and stochasticity remains poorly understood. Mitochondria are an important regulator of intracellular Ca 2+ dynamics in several cell types such as pancreatic acinar cells. It has thus been hypothesized that mitochondria are an important modulator of Ca 2+ pulsar. Mitochondrial influence on Ca 2+ pulsar was explored on cut‐opened mesenteric resistance arteries using a high‐speed confocal microscope. Inhibition of mitochondrial uniporter‐dependent Ca 2+ uptake (Ru360) increased the surface covered by a Ca 2+ pulsar (+30%). Conversely, stimulation of mitochondrial Ca 2+ uptake (kaempferol) reduced Ca 2+ pulsar's spreading (−20%), suggesting that mitochondria could limit Ca 2+ pulsars propagation. Interestingly, inhibition of mitochondrial Ca 2+ efflux (CsA for mPTP; CGP37157 for NCLX) had little if any effect on spatial dispersion of a Ca 2+ pulsar. However, de novo Ca 2+ pulsar sites were observed following exposure to CsA/CGP. Mitochondria might thus control subcellular Ca 2+ levels within MEP to modulate IP 3 R activity. Electron microscopy showed clustering of mitochondrial distribution near the MEP. These results suggest that mitochondria might play a significant role in regulating local endothelial Ca 2+ signalling and then, modulate vascular tone. Support or Funding Information FRQS, CFI, SQHA 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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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".