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 ?M). 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 ?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.