Abstract 12665: Remodeling of Nuclear Ca <sup>2+</sup> Disposition in Atrial Fibrillation Associated Remodeling
Bibliographic record
Abstract
Introduction: Atrial fibrillation (AF) induces substantial self-promoting remodeling related to the rapid atrial rate. There is evidence that changes in nuclear Ca 2+ content alter ion channel gene expression and thereby effect electrophysiological changes that increase AF vulnerability and maintenance. However, the ways in which AF affects atrial cardiomyocyte (ACM) nuclear Ca 2+ disposition are unknown. Here, we studied the effects of AF-related remodeling on ACM nuclear structure and Ca 2+ handling. Methods and Results: ACMs were isolated from control (CTL) dogs and dogs subjected to 1 week of AF maintained by atrial tachypacing at 600 bpm (n=7, 6 respectively). We used nuclear imaging with Fluo-5N AM and nucleoplasmic and cytoplasmic calcium transient (CaT) recordings from intact ACMs loaded with Fluo-4 AM. AF significantly decreased the number of nuclear invaginations (NIV) normalized to nuclear envelope (NE) circumference, and increased nuclear length and perimeter in ACMs (Figure A). Diastolic [Ca 2+ ] nuc and [Ca 2+ ] cyto increased in AF vs CTL (Figure B, by 110%*, 89%* respectively, *P<0.05). Nucleoplasmic Ca 2+ transient amplitude decreased significantly with AF, but simultaneously measured cytoplasmic transient amplitude did not change (Figure C). Relaxation time from peak of the Ca 2+ transient to 50% decline (TD 50 ) of nucleoplasmic and cytoplasmic CaTs were significantly prolonged in AF. The addition of a physiological nuclear Ca 2+ transient enhancer, endothelin (200 nM), increased diastolic [Ca 2+ ] nuc and [Ca 2+ ] cyto in both CTL (by 25±6%, 21±6%) and AF (by 40±4%, 31±2 ) ACMs. The IP3 receptor blocker 2-aminoethoxydiphenyl borate (2-APB, 5 μM) abolished endothelin effects on [Ca 2+ ] nuc . Conclusions: AF-related remodeling alters atrial cardiomyocyte nuclear structure and nucleoplasmic [Ca 2+ ] handling. These alterations may play an important role in associated gene-expression changes that produce the AF substrate.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".