SK channels are involved in the stimulation of intracellular Ca <sup>2+</sup> signals by reactive oxygen species (ROS) in intact endothelium
Bibliographic record
Abstract
Increased production of ROS such as superoxide anions (O2−) is associated with endothelial dysfunction encountered in cardiovascular pathologies. An elevation of intracellular Ca2+ levels ([Ca2+]i) has been reported in cultured endothelium exposed to high concentration of ROS. However, the impact of O2− on [Ca2+]i dynamics remains to be determined in native endothelium. Therefore, the effects of O2− on Ca2+ signals in the endothelium of cut-open mesenteric arteries from mouse were investigated, using fluo-4 and laser scanning confocal microscopy. Endothelial cells in this preparation exhibit a variety of spontaneous Ca2+ signals (waves and oscillations). Catalase (500 U/ml) had little, if any, effect on basal [Ca2+]i or Ca2+ signals. In contrast, exposure to superoxide dismutase (SOD) (100 U/ml) decreased by 50% the frequency of spontaneous activity. Exposure to O2− caused a rise in global Ca2+ levels, along with a 2- to 3-fold increase in amplitude and frequency of Ca2+ waves, sustained for at least 10 min. The stimulatory effects of O2− on Ca2+ signals did not require extracellular Ca2+, but its maintenance did, suggesting a dependence on the Ca2+ electrochemical gradient. Consistently, blocking SK channels with apamin caused a membrane depolarization, and decreased the long term elevation of Ca2+ signaling by O2−. Therefore, basal production of O2−, but not H2O2, stimulates intracellular Ca2+ signaling in intact endothelium. Furthermore, sustained effects of O2− on [Ca2+]i and its dynamics requires extracellular Ca2+ entry, which is modulated by SK channel-regulation of endothelial membrane potential. Supported by NIH (HL63722 & HL44455) 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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".