THYROIDAL ENHANCEMENT OF RAT MYOCARDIAL NA,K-ATPASE - PREFERENTIAL EXPRESSION OF ALPHA-2 ACTIVITY AND MESSENGER-RNA ABUNDANCE

In hypothyroid rat myocardium, the low-ouabain-sensitivity Na,K-ATPase activity had a Ki=10-4m and accounted for ∼95% of the enzyme activity, while the high-ouabain-sensitivity activity contributed ∼5% to the total activity, with a Ki=3×107m. mRNAα1 was 7.2- and 5.5-fold more abundant than mRNAα2 and mRNAβ, respectively, in hypothyroid ventricles while mRNAα3 was undetectable. Administration of T3 increased total Na,K-ATPase activity 1.6-fold; the low-ouabain-sensitivity activity increased 1.5-fold while high-ouabain-sensitivity activity was stimulated 3.2-fold. T3 increased the number of high-affinity ouabain-binding sites 2.9-fold with no change in Kd (∼2×10-7m). The abundances of mRNAα1, mRNAα2, and mRNAβ (per unit RNA) following T3 treatment increased 3.6-, 10.6-, and 12.7-fold, respectively. The larger increments in subunit mRNA abundances than in Na,K-ATPase activity suggests the involvement of translational and/or post-translational regulatory steps in Na,K-ATPase biogenesis in response to T3. It is concluded that T3 enhances myocardial Na,K-ATPase subunit mRNA abundances and Na,K-ATPase activity, and that the expression of the high- and low-ouabain-sensitivity activities are probably a reflection of the abundances of the α2 and α1 isoforms, respectively. The physiological role played by the β subunit remains uncertain. © 1990 Springer-Verlag New York Inc.