Hypoxia reduces the function and expression of hERG potassium channels (887.2)
Bibliographic record
Abstract
Human ether‐a‐go‐go‐related gene (hERG) encodes the pore‐forming subunit of the I Kr channel which is important for cardiac repolarization. Loss of function of the hERG channel due to mutations or drugs causes long QT syndrome, a cardiac disorder with high risk of cardiac arrhythmias and sudden death. Obstructive Sleep Apnea (OSA) patients who experience intermittent hypoxia display an increased incidence of cardiac arrhythmias. We recently found that OSA patients display a trend of reduced hERG expression in atrial tissues. In the present study, we demonstrate that hypoxic culture (0.5% O 2 ) of neonatal rat cardiomyocytes for 24 h reduced I Kr by 80%. However, the same treatment did not affect the amplitudes of Na + current, Ca 2+ current, the transient outward K + current (I to ) and the inward rectifier K + current (I K1 ). Hypoxic culture (0.5% O 2 ) decreased the abundance of hERG channels expressed in HEK 293 cells along with an enhanced expression of HIF1‐ (Hypoxia‐Inducible Factor) which is known to up‐regulate various proteins including proteolytic enzymes. Chemically inducing HIF1‐ by using cobalt chloride also decreased hERG expression. Protease inhibitors including leupeptin (100µM) completely abolished the hypoxic‐induced reduction in hERG expression. Our data raised the possibility that hypoxia decreases hERG expression by activating certain proteases, which degrade the channel protein. Supported by the Canadian Institutes of Health Research ‐ CIHR Grant Funding Source : supported by: CIHR
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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".