Diastolic calcium is elevated in metabolic recovery of cardiomyocytes expressing elevated levels of the Na<sup>+</sup>/H<sup>+</sup>exchanger
Bibliographic record
Abstract
In the myocardium, the Na+/H+ exchanger isoform 1 (NHE1) plays a pivotal role in mediating ischemia-reperfusion (I/R) injury by causing intracellular Na+ accumulation that results in a subsequent increase in intracellular calcium (Ca2+ overload). One of the major clinical correlates of I/R injury is contractile dysfunction, in which Ca2+ overload via increased Na+/Ca2+ exchange is a major contributor. To better understand the cellular role of NHE1 during I/R injury, contractile function and calcium transients were measured during metabolic inhibition and recovery in single ventricular myocytes from transgenic mice with elevated NHE1 expression. During normoxic conditions, no differences were seen between NHE1-overexpressing cardiomyocytes and wild-type (WT) cardiomyocytes with respect to fractional cell shortening (FCS), rate of shortening (+dL/dt), and rate of relaxation (-dL/dt). When metabolic recovery followed metabolic inhibition, NHE1-overexpressing ventricular myocytes exhibited a significant increase in FCS (130.2% +/- 11.77% baseline) and +/-dL/dt (146.93% +/- 12.27% baseline). This correlated with a significant increase in the concentration of diastolic intracellular calcium, which was attenuated by the NHE1 inhibitor HOE694. These results indicate that in normoxic conditions, elevated NHE1 expression does not alter contractile function. During metabolic recovery, however, elevated NHE1 expression increased diastolic Ca2+ loading that led to augmented cell contractility.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 teacher head, 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".