Asynchronous Ca <sup>2+</sup> Waves in Intact Venous Smooth Muscle
Bibliographic record
Abstract
The rabbit inferior vena cava (IVC) is a large-capacitance vessel that displays typical contractile dose-response curves for caffeine and phenylephrine (PE). Using confocal microscopy on the endothelium-denuded IVC, we undertook experiments to correlate these whole-tissue contractile dose-response curves with changes in subcellular [Ca(2+)](i) signals in the in situ vascular smooth muscle cells (VSMCs). We observed that both caffeine and PE initially elicited Ca(2+) waves in individual VSMCs. The [Ca(2+)](i) in cells challenged with caffeine subsequently returned to baseline whereas the [Ca(2+)](i) in cells challenged with PE exhibited repetitive asynchronous Ca(2+) waves. These [Ca(2+)](i) oscillations were related to Ca(2+) release from the sarcoplasmic reticulum as they were inhibited by ryanodine and caffeine. The lack of synchronicity of the [Ca(2+)](i) oscillations between VSMCs can explain the observed tonic contraction at the whole-tissue level. The nature of these Ca(2+) waves was further characterized. For caffeine, the amplitude was all-or-none in nature, with individual cells differing in sensitivity, leading to their recruitment at different concentrations of the agonist. This concentration dependency of recruitment appears to form the basis for the concentration dependency of caffeine-induced contraction. Furthermore, the speed of the Ca(2+) waves correlated positively with the concentration of caffeine. In the case of PE, we observed the same characteristics with respect to wave speed, amplitude, and recruitment. Increasing concentrations of PE also enhance the frequency of the [Ca(2+)](i) oscillations. We therefore conclude that PE stimulates whole-tissue contractility through differential recruitment of VSMCs and enhancement of the frequency of asynchronous [Ca(2+)](i) oscillations once the cells are recruited.
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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 | 0.001 |
| 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) | 0.003 | 0.001 |
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; both teacher heads agree on what is shown here.
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".