Cardiomyocyte ryanodine receptor clusters expand and coalesce after application of isoproterenol
Bibliographic record
Abstract
Earlier work has shown that ventricular ryanodine receptors (RyR2) within a cluster rearrange on phosphorylation as well as with a number of other stimuli. Using dSTORM, we investigated the effects of 300 nmol/liter isoproterenol on RyR2 clusters. In rat ventricular cardiomyocytes, there was a symmetrical enlargement of RyR2 cluster areas, a decrease in the edge-to-edge nearest neighbor distance, and distribution changes that suggested movement to increase the cluster areas by coalescence. The surface area covered by the phosphorylated clusters was significantly greater than in the control cells, as was the cluster density. This latter change was accompanied by a decreased cluster fragmentation, implying that new tetramers were brought into the sarcoplasmic reticulum. We propose a possible mechanism to explain these changes. We also visualized individual RyR2 tetramers and confirmed our earlier electron-tomographic finding that the tetramers are in a disorganized but non-random array occupying about half of the cluster area. Multiclusters, cluster groups defined by the maximum distance between their members, were analyzed for various distances. At 100 nm, the areas occupied by the multiclusters just exceeded those of the single clusters, and more than half of the multiclusters had only a single subcluster that could initiate a spark. Phosphorylation increased the size of the multiclusters, markedly so for distances >100 nm. There was no relationship between the number of subclusters in a group and the area covered by it. We conclude that isoproterenol induces rapid, significant, changes in the molecular architecture of excitation-contraction coupling.
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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) | 0.001 | 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 | 0.001 |
| 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".