Function of Ca <sup>2+</sup> Release Channels in Purkinje Cells That Survive in the Infarcted Canine Heart
Bibliographic record
Abstract
BACKGROUND: Triggered Purkinje ectopy can lead to the initiation of serious ventricular arrhythmias in post-myocardial infarction patients. In the canine model, Purkinje cells from the subendocardial border of the healing infarcted heart can initiate ventricular arrhythmias. Intracellular Ca(2+) abnormalities underlie these arrhythmias, yet the subcellular reasons for these abnormalities remain unknown. METHODS AND RESULTS: Using 2D confocal microscopy, we directly quantify and compare typical spontaneous Ca(2+) events in specific subcellular regions of normal Purkinje cells with those Purkinje cells from the subendocardium of the 48-hour infarcted canine heart (IZPCs). The Ca(2+) event rate was higher in the subsarcolemmal region of IZPCs when compared with normal Purkinje cells; IZPC amplitudes were higher, yet the spatial extents of these events were similar. The amplitude of caffeine-releasable Ca(2+) in either the subsarcolemmal or core regions of IZPCs did not differ from normal Purkinje cells, suggesting that Ca(2+) overload was not related to the frequency change. In permeabilized Purkinje cells from both groups, the event rate was related to free [Ca(2+)] in both subsarcolemmal and core, but in IZPCs, this event rate was significantly increased at each free Ca(2+), suggesting an enhanced sensitivity to Ca(2+) release. Furthermore, decays of wide long lasting Ca(2+) release events in IZPC's core were significantly accelerated compared with those in normal Purkinje cells. JTV519 (K201) suppressed IZPC cell wide Ca(2+) waves as well as normalized the enhanced event rate and its response to free Ca(2+). CONCLUSIONS: Increased spontaneous Ca(2+) release events in IZPCs are due to uniform regionally increased Ca(2+) release channel sensitivity to Ca(2+) without a change in sarcoplasmic reticulum content. In addition, Ca(2+) reuptake in IZPCs is accelerated. These properties would lower the threshold of Ca(2+) release channels, setting the stage for the highly frequent arrhythmogenic cell wide Ca(2+) waves observed in IZPCs.
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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 | 0.001 |
| 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".