Caveolae Link Ca <sub>V</sub> 3.2 Channels to BK <sub>Ca</sub> -Mediated Feedback in Vascular Smooth Muscle
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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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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it