Endothelin-1 Regulates Cytosolic and Nuclear Ca2+ in Human Endocardial Endothelium
Bibliographic record
Abstract
Endocardial endothelium is far less studied than its systemic and pulmonary counterparts and its role in cardiac function is not well known. In the study reported here, we succeeded in isolating and culturing endocardial endothelial cells (EECs) from 21-week-old human fetal heart and verified whether endothelin-1 (ET-1) receptors are present on these cells and whether their activation regulates cytosolic ([Ca]c) and nuclear calcium ([Ca]n). Using fluo-3 Ca2+ measurement and three-dimension confocal microscopy techniques, superfusion of fetal human EECs from right and left ventricles with increasing concentrations of ET-1 induced a dose-dependent sustained increase of free cytosolic and nuclear Ca2+ levels with an EC50 near 10(-10) M and 10(-11) M, respectively. The sustained increase of cytosolic and nuclear Ca2+ by ET-1 in both EEC preparations was completely blocked by the calcium chelator ethylene glycol-bis (beta-aminoethylether)-N,N,N',N'-tetra-acetic acid (EGTA) but was insensitive to the L-type Ca2+ channel blocker, nifedipine. The effect of ET-1 was prevented by the ET(A)-receptor antagonist BQ 123. However the ET(B)-receptor antagonist BQ 788 had no effect. Our results suggest that ET-1 receptors are present in human EECs and that their stimulation induces sustained Ca2+ influx through ET(A)-receptor stimulation of a nifedipine-insensitive Ca2+ channel, probably the R-type Ca2+ channel. The presence of Ca2+-dependent responses to ET-1 supports a possible modulatory role of the endocardial endothelium in myocardial functions.
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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".