C-Terminus of Cav1.3 L-Type Ca2+ Channel Upregulates Its Own Gene Expression
Bibliographic record
Abstract
Introduction: Ca v 1.3 L‐type calcium (Ca 2+ ) channel plays a critical role in cardiac excitation-contraction coupling, regulating heart rate, contractility, and gene expression. The C-terminus of Ca v 1.3 has recently been shown to translocate to the nucleus and act as a transcriptional factor to modulate the function of Ca 2+ activated K + channels in atrial cardiomyocytes. However, the role of Ca v 1.3-C-terminus in the regulation of transcription of its own Ca v 1.3 gene remains unknown. Methods and Results : We evaluated the impact of the nuclear translocation of Ca v 1.3-C-terminus on the transcription of Ca v 1.3 gene and Ca v 1.3 promoter activity in vitro using cultured neonate rat ventricular myocytes (NRVMs), and mouse atrial cardiomyocytes (HL-1). Lentiviral infection of NRVMs demonstrated that the cleaved Ca v 1.3-C-terminus, translocate to the nucleus where it acts as an enhancer. C-terminus of Ca v 1.3 increased transcription of Ca v 1.3 in vitro in NRVMs and in vivo in mice ventricles. Additionally, MEF2 transcription factor binding sites along the Ca v 1.3 promoter seemed to mediate the regulatory effect of the Ca v 1.3-C-terminus. Conclusion: The data are first to demonstrate unique upregulation of Ca v 1.3 transcription by its own mobile Ca v 1.3-C‐terminus both in vitro and in vivo . These novel findings are directly translatable to the development of new therapeutics aimed at increasing Ca 2+ entry into the cells via intrinsic Ca v 1.3 gene expression upregulation such as in heart failure where additional and optimal Ca 2+ entry could be beneficial.
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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) | 0.003 | 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".