Mitochondria Modulates Calcium Pulsars Kinetics in Native Endothelial Cells from Mouse Mesenteric Arteries
Bibliographic record
Abstract
Endothelial control of vascular tone is modulated by local calcium (Ca 2+ ) signaling events like Ca 2+ pulsars, an IP 3 R‐dependant Ca 2+ release restricted to myoendothelial projections (MEP). Aside from the recent report of Ca 2+ pulsars being modulated by CaMKII, mechanisms regulating endothelial spontaneous Ca 2+ release remain unidentified. Mitochondria are important modulators of intracellular Ca 2+ dynamics in various cell types and, we hypothesized mitochondria may control endothelial Ca 2+ pulsars. High‐speed confocal microscopy was used to investigate mitochondria's influence on endothelial Ca 2+ pulsar in cut‐open mouse mesenteric arteries ( en face configuration). Preventing mitochondrial Ca 2+ uptake by uncoupling with FCCP uncovered a new Ca 2+ pulsar site population that had a lower frequency (≈+30%) but larger diffusional spread (+57%) than controls. Inhibition of mitochondrial Ca 2+ uptake via the uniporter using Ru360 increased the spread of Ca 2+ pulsars (≈+30%), though kinetics were not significantly altered. Significantly, inhibition of mitochondrial Ca 2+ export (CGP37157, CsA) increased the number of active Ca 2+ pulsar sites, each with a decreased bursting frequency. In summary, these results suggest that mitochondrial uptake and release of Ca 2+ acts as a critical local modulator of Ca 2+ pulsar kinetics and may therefore be crucial to endothelial control of vascular tone. Support or Funding Information FRQS, HSFC, 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) | 0.000 | 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 | 0.001 |
| 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 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".