Amiodarone Inhibits the 3,5,3′-Triiodothyronine-Dependent Increase of Sodium/Potassium Adenosine Triphosphatase Activity and Concentration in Human Atrial Myocardial Tissue

In animal models the function of the sodium pump (sodium/potassium-adenosine triphosphatase [Na⁺/K⁺-ATPase]) is enhanced by 3,5,3′-triiodothyronine (T₃) and inhibited by the antiarrhythmic agent amio. However, it is still unclear whether the effect of the drug on Na⁺/K⁺-ATPase depends on the interference with thyroid hormone action. We evaluated the interaction of T₃ with amiodarone on Na⁺/K⁺-ATPase activity and site number in human myocardium. Right atrial slices were cultured with(T₃ ⁺) and without (T₃ ^-) 3 nM T₃ in presence and absence of amiodarone at therapeutical dose (1.5 μM). When compared to T₃ ⁺, T₃ ^- preparations showed decreased ³H-ouabain binding(p < 0.004) and lower 20-minute and 45-minute ⁸⁶Rb-uptake (p ≤ 0.004). Amiodarone caused an average 49% reduction of the T₃-dependent ³H-ouabain binding and decreased the Western blot signal for the Na⁺/K⁺-ATPase α ₁ subunit. The drug also inhibited T₃-dependent increase in ⁸⁶Rb-influx at 20 and 45 minutes by 66% and 42%, respectively, without affecting the affinity of the pump for K⁺. No differences were found in the ³H-ouabain binding and ⁸⁶Rb-uptake of T₃ ^-, T₃ ^- amio and T₃ ⁺-amio. In conclusion, T₃ stimulates the Na⁺/K⁺-ATPase in human atrial myocardium by increasing the number of ouabain-binding sites, whereas amiodarone decreases the sodium pump function secondarily to the antagonism with thyroid hormone.