Thyroidal enhancement of rat myocardial Na,K-ATPase: Preferential expression of α2 activity and mRNA abundance

Abstract

In hypothyroid rat myocardium, the low-ouabain-sensitivity Na,K-ATPase activity had aK _i =10⁻⁴ m and accounted for ∼95% of the enzyme activity, while the high-ouabain-sensitivity activity contributed ∼5% to the total activity, with aK _i =3×10⁷ m. mRNA_α1 was 7.2- and 5.5-fold more abundant than mRNA_α2 and mRNA_β, respectively, in hypothyroid ventricles while mRNA_α3 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 inK _d (∼2×10⁻⁷ m). The abundances of mRNA_α1, mRNA_α2, and mRNA_β (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.