Cardiac Ion Channel Expression and Contractile Function in Mice with Deletion of Thyroid Hormone Receptor or
Bibliographic record
Abstract
Cardiac myocytes express the two thyroid hormone receptors (T3Rs), T3Rα and T3Rβ. However, which isoform contributes to specific, T3-induced alterations of cardiac function remains unclear. Here, we used individual T3R isoform knockout (KO) mice to study the effects of T3Rα and T3Rβ in the heart. Our findings indicate that potassium channel genes that code for K+ channels involved in action potential repolarization, like KV 4.2 and minK, are T3Rα targets. Both are markedly regulated by thyroid status. The recently identified cyclic nucleotide-gated channels, HCN2 and HCN4, are targets of T3Rα and are unchanged in a euthyroid T3Rβ KO. However, these transcripts respond markedly to altered T3 signaling concomitant with bradycardia in T3Rα KO and hypothyroid animals, as well as tachycardia in hyperthyroid T3Rβ KO mice. SERCA2a and myosins are T3 regulated and were also targets of T3Rα, and the papillary muscles of αKO animals showed a slowed rate of force development. Because of the absence of significant cardiac effects in euthyroid T3Rβ KO mice, we determined messenger RNA levels for both T3Rα and T3Rβ in the heart. We found that T3Rβ is present at a 1:3 ratio to T3Rα1. We conclude that the cardiac phenotype regulated by T3 is predominantly mediated by T3Rα and that the lack of T3Rα cannot be compensated by T3Rβ in the heart.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".