Mechanism of asynchronous Ca<sup>2+</sup>waves underlying agonist‐induced contraction in the rat basilar artery
Bibliographic record
Abstract
BACKGROUND AND PURPOSE: Uridine 5'-triphosphate (UTP) is a potent vasoconstrictor of cerebral arteries and induces Ca(2+) waves in vascular smooth muscle cells (VSMCs). This study aimed to determine the mechanisms underlying UTP-induced Ca(2+) waves in VSMCs of the rat basilar artery. EXPERIMENTAL APPROACH: Isometric force and intracellular Ca(2+) ([Ca(2+)](i)) were measured in endothelium-denuded rat basilar artery using wire myography and confocal microscopy respectively. KEY RESULTS: Uridine 5'-triphosphate (0.1-1000 micromol.L(-1)) concentration-dependently induced tonic contraction (pEC(50) = 4.34 +/- 0.13), associated with sustained repetitive oscillations in [Ca(2+)](i) propagating along the length of the VSMCs as asynchronized Ca(2+) waves. Inhibition of Ca(2+) reuptake in sarcoplasmic reticulum (SR) by cyclopiazonic acid abolished the Ca(2+) waves and resulted in a dramatic drop in tonic contraction. Nifedipine reduced the frequency of Ca(2+) waves by 40% and tonic contraction by 52%, and the nifedipine-insensitive component was abolished by SKF-96365, an inhibitor of receptor- and store-operated channels, and KB-R7943, an inhibitor of reverse-mode Na(+)/Ca(2+) exchange. Ongoing Ca(2+) waves and tonic contraction were also abolished after blockade of inositol-1,4,5-triphosphate-sensitive receptors by 2-aminoethoxydiphenylborate, but not by high concentrations of ryanodine or tetracaine. However, depletion of ryanodine-sensitive SR Ca(2+) stores prior to UTP stimulation prevented Ca(2+) waves. CONCLUSIONS AND IMPLICATIONS: Uridine 5'-triphosphate-induced Ca(2+) waves may underlie tonic contraction and appear to be produced by repetitive cycles of regenerative Ca(2+) release from the SR through inositol-1,4,5-triphosphate-sensitive receptors. Maintenance of Ca(2+) waves requires SR Ca(2+) reuptake from Ca(2+) entry across the plasma membrane via L-type Ca(2+) channels, receptor- and store-operated channels, and reverse-mode Na(+)/Ca(2+) exchange.
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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".