Regulation of Connexin43 by NHE1 in Phenylephrine‐Induced Cardiomyocyte Hypertrophy
Bibliographic record
Abstract
Connexin 43, the major gap junction protein expressed in cardiac ventricular cells, undergoes changes in distribution and expression levels in cardiac diseases. The Na‐H exchanger (NHE1), a key mediator of hypertrophy and heart failure, is colocalized with Cx43 in cardiac cells. Neonatal rat myocytes were treated with phenylephrine (PE) for 24 hours to induce hypertrophy. Increased Cx43 expression observed with PE treatment (35 ± 6% compared to control) was further significantly augmented by the NHE1 inhibitor EMD87580 (75 ± 9 % compared to control). As assessed with confocal microscopy, the observed diffuse distribution of Cx43 in the presence of PE was partially reversed with the addition of EMD. EMD prevented PE induced hypertrophy and JNK1/2 activation whereas inhibition of JNK1/2 significantly increased PE‐induced upregulation of Cx43 protein levels (40 ± 10 % vs 80 ± 9% with JNK inhibition). Inhibition of reverse mode Na‐Ca exchange (NCX) with KB‐R7943 partially reversed JNK1/2 activation (95 ± 21% vs 45 ± 14% with KB) and augmented upregulation of Cx43 protein (25 ± 9% vs 100 ± 29% with KB) in the presence of PE. Our results demonstrate that NHE1 negatively regulates Cx43 protein expression via JNK1/2 in PE‐induced cardiomyocyte hypertrophy. Increased intracellular Ca levels due to reverse mode NCX may be the link between NHE1 and activation of JNK1/2. This work is funded by the HSFO Program in Heart Failure and 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 | 0.001 |
| 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".