Amiodarone Decreases Na,K-ATPase α2 and β2 Expression Specifically in Cardiac Ventricle

Studies have suggested that chronic amiodarone treatment (a class III antiarrhythmic) may have effects on the myocardium that resemble those of hypothyroidism. Since hypothyriodism is associated with decreased expression of Na,K-ATPase α1, α2 and β1 subunits in heart and α2 subunit in skeletal muscle, we aimed to test the hypothesis that chronic in vivo administration of amiodarone would result in changes in the expression of Na,K-ATPase isoforms that resembled those seen in hypothyroid rat. Rats were treated with 40 μg/g body weight amiodarone for 3 and 6 weeks. Na,K-ATPase α1, α2, β1 mRNA and protein levels and β2 mRNA were measured in cardiac ventricle and skeletal muscle. After 3 weeks of amiodarone cardiac α1, α2 and β1 protein levels were decreased to 0.65, 0.42, and 0.54 of control, respectively. After 6 weeks of treatment, cardiac α1 and β1 levels returned to control and α2 remained depressed. At the mRNA level α2 and β2 decreased to 0.6-fold of control after 6 weeks treatment. There was no effect of amiodarone on skeletal muscle Na,K-ATPase expression at either time point. We conclude that the effects of amiodarone on myocardial Na,K-ATPase expression are similar to those of hypothyroidism after 3 weeks of amiodarone treatment, but by 6 weeks the similarities are limited to the decrease in α2 and β2 expression. The lack of effect of α1 and β1 expression in heart at 6 weeks, and lack of effect on skeletal muscle Na,K-ATPase expression, all seen in hypothyroidism, indicate that amiodaroneʹs actions are isoform and tissue specific.