Increased spontaneous Ca <sup>2+</sup> activity in Cardiac Purkinje cells after myocardial infarction; A consequence of a dramatic shift of SERCA isoforms as potential adaptation to acute ischemia?
Bibliographic record
Abstract
Abstract Background Studies of Purkinje cells (Pcells) from canine hearts have suggested an increase of Ca 2+ -release by the sarcoplasmic reticulum (SR) but also reported a potential augmentation of SR-Ca 2+ -uptake after MI. Abnormal increase of SR-Ca 2+ -uptake in heart cells is novel and contrasts with the reduction of this function in cells of failing heart. Our study examined the origin of this increased SR-Ca 2+ -uptake by considering a change in SR-Ca 2+ pump (SERCA2) expression in Purkinje fibers (PFs) post MI. Methods Pcells were isolated from canine hearts 48Hrs post MI. Intracellular Ca 2+ -activity was captured by confocal microscopy. Purkinje-typical Ca 2+ events were analyzed to probe the regional Ca 2+ -dynamics within Pcells. A Purkinje-specific numerical model assisted in the interpretation of Ca 2+ -anomalies detected in Pcells Ca 2+ -transients. SR-Ca 2+ -uptake system was studied by immunofluorescence in Pcells from canine, ovine and human hearts post MI. SERCA protein and gene expressions in PFs and myocardium were measured by Western Blots and RT-qPCR in a classical porcine model of MI. Results 48Hrs after MI, Pcells showed 60% increase in spark-rate and 37% acceleration of Ca 2+ wave decay. In the model of normal wave, 35% increase of Ca 2+ -uptake rate reproduced the actual post-MI wave alterations. In apparent contrast with increased Ca 2+ -uptake rate, SERCA2 protein expression was reduced in canine, sheep, and human Pcells after MI. In pig MI model, the protein level of cardiac-specific SERCA2-splicing variant SERCA2a was reduced by 52% in the whole infarcted ventricle whereas the “non-cardiac” SERCA2b level was increased by 120%. In the infarcted regions, PFs showed 30% downregulation of SERCA2a gene expression and 630% upregulation of SERCA2b. Conclusion Our results confirm that elevated spontaneous Ca 2+ -activity in post-MI PFs is due to increased SR-Ca 2+ -uptake within Pcells. Data suggest that a replacement of “cardiac” SERCA2a by the “non-cardiac” SERCA2b sub-isoform in cardiac cells in response to ischemia is implicated in this alteration.
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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) | 0.001 | 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".