Insensitivity of cardiac delayed‐rectifier <i>I</i><sub>Kr</sub> to tyrosine phosphorylation inhibitors and stimulators
Bibliographic record
Abstract
1. The rapidly activating delayed-rectifying K+ current (I(Kr)) in heart cells is an important determinant of repolarisation, and decreases in its density are implicated in acquired and inherited long QT syndromes. The objective of the present study on I(Kr) in guinea-pig ventricular myocytes was to evaluate whether the current is acutely regulated by tyrosine phosphorylation. 2. Myocytes configured for ruptured-patch or perforated-patch voltage-clamp were depolarised with 200-ms steps to 0 mV for measurement of I(Kr) tail amplitude on repolarisations to -40 mV. 3. I(Kr) in both ruptured-patch and perforated-patch myocytes was only moderately (14-20%) decreased by 100 microM concentrations of protein tyrosine kinase (PTK) inhibitors tyrphostin A23, tyrphostin A25, and genistein. However, similar-sized decreases were induced by PTK-inactive analogues tyrphostin A1 and daidzein, suggesting that they were unrelated to inhibition of PTK. 4. Ruptured-patch and perforated-patch myocytes were also treated with promoters of tyrosine phosphorylation, including phosphotyrosyl phosphatase (PTP) inhibitor orthovanadate, exogenous c-Src PTK, and four receptor PTK activators (insulin, insulin-like growth factor-1, epidermal growth factor, and basic fibroblast growth factor). None of these treatments had a significant effect on the amplitude of I(Kr). 5. We conclude that Kr channels in guinea-pig ventricular myocytes are unlikely to be regulated by PTK and PTP.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".