Cardiac Na<sup>+</sup>–Ca<sup>2+</sup> exchanger current induced by tyrphostin tyrosine kinase inhibitors
Bibliographic record
Abstract
Tyrosine kinase (TK) inhibitors genistein and tyrphostin A23 (A23) inhibited Ca(2+) currents in guinea-pig ventricular myocytes investigated under standard whole-cell conditions (K(+)-free Tyrode's superfusate; EGTA-buffered (pCa-10.5) Cs(+) dialysate). However, the inhibitors (100 microM) also induced membrane currents that reversed between -40 and 0 mV, and the objective of the present study was to characterize these currents. Genistein-induced current behaved like Cl(-) current, and was unaffected by either the addition of divalent cations (0.5 mM Cd(2+); 3 mM Ni(2+)) that block the Na(+)-Ca(2+) exchanger (NCX), or the removal of external Na(+) and Ca(2+). A23-induced current was independent of Cl(-) driving force, and strongly suppressed by addition of Cd(2+) and Ni(2+), and by removal of either external Na(+) or Ca(2+). These and other results suggested that A23 activated an NCX current driven by submembrane Na(+) and Ca(2+) concentrations higher than those in the bulk cytoplasm. Improved control of intracellular Na(+) and Ca(2+) concentrations was obtained by suppressing cation influx (10 microM verapamil) and raising dialysate Na(+) to 7 mM and dialysate pCa to 7. Under these conditions, stimulation by A23 was described by the Hill equation with EC(50) 68 +/- 4 microM and coefficient 1.1, tyrphostin A25 was as effective as A23, and TK-inactive tyrphostin A1 was ineffective. Phosphotyrosyl phosphatase inhibitor orthovanadate (1 mM) antagonized the action of 100 microM A23. The results suggest that activation of cardiac NCX by A23 is due to inhibition of genistein-insensitive TK.
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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) | 0.002 | 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".