Caveolae Link Ca <sub>V</sub> 3.2 Channels to BK <sub>Ca</sub> -Mediated Feedback in Vascular Smooth Muscle
Bibliographic record
Abstract
Objective— This study examined whether caveolae position Ca V 3.2 (T-type Ca2+ channel encoded by the α-3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca 2+ influx to trigger Ca 2+ sparks and large-conductance Ca 2+ -activated K + channel feedback. Approach and Results— Using smooth muscle cells from mouse mesenteric arteries, the proximity ligation assay confirmed that Ca V 3.2 reside within 40 nm of caveolin 1, a key caveolae protein. Methyl-β-cyclodextrin, a cholesterol depleting agent that disrupts caveolae, suppressed Ca V 3.2 activity along with large-conductance Ca 2+ -activated K + –mediated spontaneous transient outward currents in cells from C57BL/6 but not Ca V 3.2 −/− mice. Genetic deletion of caveolin 1, a perturbation that prevents caveolae formation, also impaired spontaneous transient outward current production but did so without impairing Ca 2+ channel activity, including Ca V 3.2. These observations indicate a mistargeting of Ca V 3.2 in caveolin 1 −/− mice, a view supported by a loss of Ni 2+ -sensitive Ca 2+ spark generation and colocalization signal (Ca V 3.2-RyR) from the proximity ligation assay. Vasomotor and membrane potential measurements confirmed that cellular disruption of the Ca V 3.2-RyR axis functionally impaired the ability of large-conductance Ca 2+ -activated K + to set tone in pressurized caveolin 1 −/− arteries. Conclusions— Caveolae play a critical role in protein targeting and preserving the close structural relationship between Ca V 3.2 and RyR needed to drive negative feedback control in resistance arteries.
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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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".