Modulation of Ca <sup>2+</sup> Release in Cardiac Myocytes by Changes in Repolarization Rate
Bibliographic record
Abstract
The early rate of action potential (AP) repolarization varies in the mammalian heart regionally, during development, and in disease. We used confocal microscopy to assess the effects of changes in repolarization rate on spatially resolved sarcoplasmic reticulum (SR) Ca(2+) release. The kinetics and peak amplitude of Ca(2+) transients were reduced, and the amplitude, frequency, and temporal synchronization of Ca(2+) spikes decreased as the rate of repolarization was slowed. The first latencies and temporal dispersion of Ca(2+) spikes tracked closely with the time to peak and the width of the L-type Ca(2+) current (I(Ca,L)), suggesting that the effects of repolarization on excitation-contraction coupling occur primarily via changes in I(Ca,L). Next, we examined the effect of changes in the rapid early repolarization rate (phase 1) of a model human AP on SR Ca(2+) release by varying the amount of transient outward K(+) current. Slowing of phase-1 repolarization also caused a loss of temporal synchrony and recruitment of Ca(2+)-release events, associated with a reduced amplitude and lengthened time to peak of I(Ca,L). Isoproterenol application enhanced and largely resynchronized SR Ca(2+) release, while it increased the magnitude and shortened the time to peak of I(Ca,L). Our data demonstrate that membrane repolarization modulates the recruitment and synchronization of SR Ca(2+) release via I(Ca,L) and illustrate a physiological role for the phase-1 notch of the AP in optimizing temporal summation and recruitment of Ca(2+)-release events. The effects of slowing phase-1 repolarization can be overcome by beta-adrenergic stimulation.
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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 | 0.001 |
| 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".