Transforming growth factor-β1 decreases cardiac muscle L-type Ca<sup>2+</sup> current and charge movement by acting on the Ca<sub>v</sub>1.2 mRNA
Bibliographic record
Abstract
Transforming growth factors-beta (TGF-betas) are essential to the structural remodeling seen in cardiac disease and development; however, little is known about potential electrophysiological effects. We hypothesized that chronic exposure (6-48 h) of primary cultured neonatal rat cardiomyocytes to the type 1 TGF-beta (TGF-beta1, 5 ng/ml) may affect voltage-dependent Ca(2+) channels. Thus we investigated T- (I(CaT)) and L-type (I(CaL)) Ca(2+) currents, as well as dihydropyridine-sensitive charge movement using the whole cell patch-clamp technique and quantified Ca(V)1.2 mRNA levels by real-time PCR assay. In ventricular myocytes, TGF-beta1 did not exert significant electrophysiological effects. However, in atrial myocytes, TGF-beta1 reduced both I(CaL) and charge movement (55% at 24-48 h) without significantly altering I(CaT), cell membrane capacitance, or channel kinetics (voltage dependence of activation and inactivation, as well as the activation and inactivation rates). Reductions of I(CaL) and charge movement were explained by concomitant effects on the maximal values of L-channels conductance (G(max)) and charge movement (Q(max)). Thus TGF-beta1 selectively reduces the number of functional L-channels on the surface of the plasma membrane in atrial but not ventricular myocytes. The TGF-beta1-induced I(CaL) reduction was unaffected by supplementing intracellular recording solutions with okadaic acid (2 microM) or cAMP (100 microM), two compounds that promote L-channel phosphorylation. This suggests that the decreased number of functional L-channels cannot be explained by a possible regulation in the L-channels phosphorylation state. Instead, we found that TGF-beta1 decreases the expression levels of atrial Ca(V)1.2 mRNA (70%). Thus TGF-beta1 downregulates atrial L-channel expression and may be therefore contributing to the in vivo cardiac electrical remodeling.
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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".