Exploiting the cellular actions of SKCa and IKCa channels to manipulate endothelial function and vascular tone
Bibliographic record
Abstract
Growing evidence indicates that small‐ and intermediate‐conductance, Ca 2+ ‐activated K + channels (SK Ca and IK Ca channels, respectively) play pivotal roles in the cellular mechanisms contributing to stimulated vasorelaxation (i.e. nitric oxide (NO) synthesis, actions of EDHF). Using single cell patch clamp and fluorimetry, along with arteriolar pressure myography, we have obtained novel results demonstrating that activators of SK Ca and IK Ca channels (i.e. NS309 and DCEBIO, 0.01 ‐ 1 μM) enhance a number of cellular processes associated with stimulated vasorelaxation (i.e. cytosolic Ca 2+ elevations, membrane hyperpolarization and NO synthesis). These observed effects of NS309 and DCEBIO were largely prevented by the SK Ca and IK Ca channel blockers apamin and TRAM‐34 in combination, but not when applied separately. In rat cremaster arterioles pressurized to 70 mmHg, NS309 and DCEBIO reduced myogenic tone and further augmented ACh‐induced vasodilation. The eNOS inhibitor L‐NAME (0.1 mM) decreased ACh‐evoked inhibition of myogenic tone, but did not affect the dilatory responses to NS309 and DCEBIO. The observed inhibition of NS309/DCEBIO action following endothelial denudation confirmed that these agents acted predominantly via the vascular endothelium. Finally, we will discuss initial efforts to discern the contribution of STIM1 to SK Ca and IK Ca activity and endothelial vasodilatory processes.
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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".