Thyroidal enhancement of rat myocardial Na,K-ATPase: preferential expression of alpha 2 activity and mRNA abundance.
In hypothyroid rat myocardium, the low-ouabain-sensitivity Na,K-ATPase activity had a KI = 10(-4) M and accounted for approximately 95% of the enzyme activity, while the high-ouabain-sensitivity activity contributed approximately 5% to the total activity, with a KI = 3 x 10(-7) M. mRNA alpha 1 was 7.2- and 5.5-fold more abundant than mRNA alpha 2 and mRNA beta, respectively, in hypothyroid ventricles while mRNA alpha 3 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 (approximately 2 x 10(-7) M). The abundances of mRNA alpha 1, mRNA alpha 2, and mRNA beta (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 alpha 2 and alpha 1 isoforms, respectively. The physiological role played by the beta subunit remains uncertain.
Gick
G G
GG
Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Melikian
J
J
Ismail-Beigi
F
F
D000818:Animals; D008297:Male; D008566:Membranes / Q000032:analysis; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis*; D014284:Triiodothyronine / Q000502:physiology*; D014316:Tritium
D012333:RNA, Messenger; D014284:Triiodothyronine; D014316:Tritium; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase