Tissue-specific isoform regulation of Na+-K+-ATPase by thyroid hormone in ferrets

Abstract

We have shown previously that in the ferret heart there are two isoforms of Na+-K+-ATPase, α(+) and α, and that these isoforms undergo developmental changes. In the present study, we examine regulation of the isoenzymes by thyroid hormone, which is well known to increase activity of Na+-K+-ATPase in different tissue preparations. Ferrets were injected with L-thyroxine (T4) (0.5 mg/kg, sc) for 3 wk. The T4-treated ferrets gained 58 ± 32 g body wt compared with 366 ± 24 g for the control ferrets. Plasma 3,5,3'-triiodothyronine concentrations of the T4-treated animals increased about eightfold 16-18 h after the last injection. The number of α(+)- and α-subunits in heart homogenates estimated by [3H]ouabain binding was 3.5 ± 0.1 and 2.5 ± 0.1 pmol/mg protein, respectively [α(+)/α = 1.40]. In the T4-treated ferrets, there was no significant increase of the α(+)-isoform (3.2 ± 0.2 pmol/mg protein), whereas the number of α-isoform increased significantly to 4.1 ± 0.3 pmol/mg protein [α(+)/α = 0.78]. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of partially purified cardiac plasma membrane preparations reveals similar pattern of changes of the isoenzymes. In the kidney, however, there was no significant change in the number of α-isoform, which is the predominant isoform in the kidney, and T4 does not appear to induce synthesis of α(+)-isoform in the kidney. It is concluded that thyroid hormone induces both isoform- and tissue specific regulation of the Na+-K+-ATPase α-subunits in the ferret. These specific regulations of the isoforms seem to suggest important physiological roles of the isoenzymes.