Reverse mode sodium‐calcium exchange (NCXrev) facilitated by co‐localization of the exchanger with TRPC channels contributes to Ca2+ influx and ER Ca2+ store refilling during agonist stimulation of endothelial cells
Bibliographic record
Abstract
The role of NCX as a mechanism for Ca 2+ entry is receiving increased attention. NCX and TRPC channels were shown to co‐localize, facilitating NCX rev mediated Ca 2+ influx in response to TRPC activation in over‐expression studies (Rosker C et al., JBC 279:13696 (2004)). Here, we employed patch clamp technique, Ca 2+ fluorimetry and co‐immunoprecipitation to determine if: 1) NCX rev contributes to Ca 2+ influx in response to agonist stimulation, and 2) TRPC and NCX are co‐localized in cultured endothelial cells (EA.Hy926). Stimulation with histamine increased steady‐state inward and outward current between −70 and +70 mV in K + ‐free solution; KB‐R7943 inhibition of NCX selectively suppressed outward current, but SKF96365 inhibition of TRPC reduced both inward and outward currents. Histamine caused an increase in Fura‐2 cytosolic Ca 2+ fluorescence and a reduction in ER Ca 2+ D1ER fluorescence. SKF96365 and KB‐R7943 suppressed the increase in cytosolic [Ca 2+ ] and enhanced the depletion of ER Ca 2+ stores induced by histamine. Significantly, TRPC1, TRPC4 and caveolin‐1 immunoreactive proteins were detected in anti‐NCX1 immunoprecipitates of endothelial cell lysates. These findings suggest that co‐localization of NCX and TRPC channels in a signaling complex in endothelial cells may facilitate Ca 2+ influx and ER Ca 2+ store refilling via NCX rev during agonist stimulation. (funded by CIHR MOP‐13505, NSERC and AHFMR).
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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".