Thyroid hormone induction of rat myocardial Na⁺-K⁺-ATPase: α₁-, α₂-, and β₁-mRNA and -protein levels at steady state

In this study, we measured the time courses of change in Na⁺-K⁺-ATPase α₁-, α₂-, and β₁-subunit mRNA and protein abundance in cardiac myocytes isolated from euthyroid, hypothyroid, and hyperthyroid (hypothyroids injected daily with 1 μg T₃/g body wt) rats. In hypothyroids, α₁-, α₂-, and β₁-protein levels were decreased to 0.55, 0.42, and 0.57 of euthyroids, predicting the decrease in Na⁺-K⁺-ATPase activity to 0.53 of control. There was no change in these subunits' mRNA levels, indicating that the decreases in protein levels were not due to decreased subunit transcription rates. In hyperthyroids, the α₁-mRNA increased to a steady state of threefold over hypothyroid by 1 day of T₃ treatment, and the α₁-protein levels increased to twofold over hypothyroid by 4 days of T₃. α₂-mRNA increased to 5-fold over hypothyroid by 2 days, whereas the α₂-protein levels increased to 14- fold above hypothyroid by 4 days of T₃. β₁-mRNA increased to 12-fold above hypothyroid by 1 day of T₃ treatment, whereas β₁-protein increased to only 2.5-fold over hypothyroid by 4 days of T₃. The discoordinate changes in α₂- and β₁-mRNA vs. protein can be reconciled with the hypothesis that β₁ is rate limiting for assembly in eu- and hypothyroids, and favors assembly with α₁, while excess unassembled α₂ is degraded. In the hyperthyroids we predict β₁ is not rate limiting and there is increased α₂β₁-assembly. We calculate that T₃ decreases the α₁-to-α₂ ratio from 24:1 in hypothyroid to 3.4:1 in hyperthyroid cardiomyocytes.