P3999Excessive activation of beta-2 adrenergic receptors induces arrhythmic calcium oscillations and ryanodine receptor phosphorylation at ser2809 but not at ser2815
Bibliographic record
Abstract
Background: Beta-adrenergic antagonists are commonly used to treat patients with myocardial diseases associated with defective calcium homeostasis such as ventricular tachycardia and heart failure. While both beta-1 and beta-2 receptors are present in the heart and modulate intracellular calcium levels, pharmacological treatments are largely based on selective beta-1 adrenergic antagonists. Purpose: We here aimed to determine how beta-2 adrenergic stimulation modulate phosphorylation of the cardiac ryanodine receptor (RyR2) and spontaneous calcium release, in order to assess their utility as a target for the control of arrhythmic calcium release. Methods: Cardiac ryanodine receptor (RyR2) phosphorylation was visualized in ventricular myocytes from transgenic mice with GFP-tagged RyR2s, using antibodies recognizing RyR2s phosphorylated at ser2809 or ser2815. The fluorescence emission in ser2809 and ser2815 labeled clusters was normalized to the GFP fluorescence emission in the corresponding clusters. RyR2 clusters were detected using a custom-made algorithm. Fluo-4 fluorescence emission was used to monitor the calcium signal in ventricular myocytes subjected to electrical field stimulation at 1 Hz. Beta-2 adrenergic receptors were activated with the selective agonist fenoterol. Protein kinase A dependent phosphorylation was inhibited with KT5720 and CaMKII dependent phosphorylation was inhibited with KN-93. KN-92 was used to assess non-specific effect of KN-93.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 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; 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".