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 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.

Thyroid Hormone Stimulates Na, K-ATPase Gene Expression in the Hemodynamically Unloaded Heterotopically Transplanted Rat Heart

“…hibit K<j values of approximately 10"4 and approximately 3 X 10"7 M toward ouabain with the a^i soform accounting Na, K-ATPase (also identified as the Na, K pump) is an for more than 90% of total Na, K-ATPase activity (4). Very ubiquitous plasma membrane protein which maintains small amounts of the a3 isoform has been detected in this the electrochemical gradients of Na+ and K+ across plasma tissue by some investigators (3,4).…”

“…Very ubiquitous plasma membrane protein which maintains small amounts of the a3 isoform has been detected in this the electrochemical gradients of Na+ and K+ across plasma tissue by some investigators (3,4). The /3-subunit is a glycomembranes of virtually all animal cells (1).…”

Thyroid hormone regulation of cardiac bioenergetics: role of intracellular creatine

“…An unpaired Student's t-test was used, and P Ͻ 0.05 was considered significant. Table 1 summarizes the effect of T 3 on body weight, heart weight, and heart weight-to-body weight ratio, with the latter parameter being a highly reliable indicator of thyroid status (5-7, 10, 14, 27, 36); the T 3 -induced hypertrophy of the heart is associated with significant increases in myocardial protein-to-DNA and RNA-to-protein ratios (7,14). As can be seen in Table 1, treatment with T 3 resulted in a dramatic increase in the heart weight-to-body weight ratio.…”

Complications of Hyperthyroidism

“…On the plasma membranes, T3 exerts direct extragenic actions on the functions other ion channels such as Na/K ATPase, Na/Ca++exchanger, and some voltage gated K channels (Kv 1.5, Kv 4.2, Kv 4.3) affecting myocardial and vascular functions [21,22] coordinating electrochemical and mechanical responses of myocardium [23,24]. It prolongs the activation of Na channels in myocardial cells [25] and induces intracellular Na uptake and secondary activation of the Na-Ca antiporter, which can partly explain the positive inotropic effect.…”