Pressure Modulation of Vascular L‐type Calcium Channels: implications to the Myogenic Response
Bibliographic record
Abstract
L‐type Ca 2+ channels govern smooth muscle [Ca 2+ ] and myogenic tone development through mechanisms traditionally tied to voltage control. While essential, questions remain as to whether voltage is the sole regulatory influence or whether L‐type Ca 2+ channels are additionally mechanosensitive. In this context, this study defined whether and by what mechanisms pressure stimuli modulate L‐type Ca 2+ channels in rodent (rat & mouse) resistance arteries. Experiments extended from single smooth muscle cells (whole‐cell/single‐channel patch clamp; immunohistochemistry; proximity ligation assay) to intact arteries (pressure myography). Whole‐cell patch clamp electrophysiology revealed that pressure stimuli increased the L‐type Ca 2+ current, a phenomenon that single channel analysis attributed to enhanced functional coupling. Subsequent work noted that pressure‐enhanced functional coupling is tied to: 1) PKC‐mediated cooperative gating; and 2) subunit trafficking to caveolae. Functional experiments, using 30 mM KCl to elicit a set depolarization (~‐40 mV), revealed that tone and cytosolic [Ca 2+ ] responses were more pronounced in arteries pressurized to 80 rather than 20 mmHg. These functional results are in alignment with patch clamp observations and suggest that L‐type Ca 2+ channels are indeed mechanosensitive. Cumulatively, our results suggest that there is more to L‐type Ca 2+ channel regulation than voltage and that pressure sensitivity must be carefully weighed in the healthy and diseased setting. Work continues to precisely define the pressure‐sensitive signaling complexes within vascular smooth muscle.
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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 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".