Effect of Altered Membranous Architecture in Vascular Smooth Muscle Contractility
Bibliographic record
Abstract
Vascular smooth muscle is the direct effector on contractility of blood vessels and is pivotal in maintaining hemodynamic stability. In response to agonist stimulations, such as neurotransmitters, hormones or drugs, the smooth muscle cell (SMC) contracts in close correspondence to the local fluctuations of intracellular calcium ions (Ca2+), which is accomplished by a sequence of repetitive Ca2+ cycling events till the agonist is removed. In brief, the Ca2+ cycles are initiated by receptors binding on the plasma membrane (PM) and followed by: (1) Ca2+ release from the sarcoplasmic reticulum (SR) to activate the contractile machinery, (2) Ca2+ entering through the PM to refill SR Ca2+ storage and (3) Ca2+ removal from the cytosol, all underly the mechanisms of local and wave‐like Ca2+ transient signals. The membranous microarchitecture and microdomain, flanked by the PM and peripheral SR, are the gates to Ca2+ entry/removal and regulate Ca2+ signals. Altered PM may compromise the encoding of the Ca2+ signal and further affect SMC contractility. The objective of this study is to investigate the functional role of the membranous microarchitecture, the caveolar domain in specific, during adrenergic stimulation. The denuded venous vascular smooth muscle was incubated with the cholesterol depleting agent, methyl‐B‐cyclodextrin (MCD), to disrupt the caveolar domain to assess the impact of the altered PM on phenylephrine (PE)‐induced contractility. We observed enhanced sensitivity to PE and a right shift of the dose‐response curve for force generation in the MCD‐treated SMC. Ultrastructurally, the MCD‐treated SMC were characterized by a wavy PM, lack of caveolar domains and enlarged peripheral SR. Notably, the frequency of the wave‐like transient Ca2+ was also enhanced by a dose‐dependent feature to PE concentrations. We believe that the intensified frequency of the wave‐like Ca2+ signal underlies the enhanced PE sensitivity in MCD‐treated SMC and disrupted caveolar domains may delay Ca2+ removal and augment SR Ca2+ retention, contributing to the intensified frequency of the Ca2+ signals. Support or Funding Information The Discovery Grant by The Natural Sciences and Engineering Research Council of Canada (NSERC)
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How this classification was reachedexpand
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) | 0.000 | 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 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".