Abstract

Amiodarone has been shown to affect cell membrane physicochemical properties, and it may produce a state of cellular hypothyroidism. Because the sarcolemmal Na⁺-K⁺ pump is sensitive to changes in cell membrane properties and thyroid status, we examined whether amiodarone affected Na⁺-K⁺pump function. We measured Na⁺-K⁺ pump current (I_p) using the whole-cell patch-clamp technique in single ventricular myocytes isolated from rabbits. Chronic treatment with oral amiodarone for 4 weeks reduced I_p when myocytes were dialyzed with patch-pipettes containing either 10 mM Na⁺ or 80 mM Na⁺. In myocytes from untreated rabbits, acute exposure to amiodarone in vitro reduced I_pwhen patch pipettes contained 10 mM Na⁺ but had no effect on I_p at 80 mM Na⁺. Amiodarone had no effect on the voltage dependence of the pump or the affinity of the pump for extracellular K⁺ either after chronic treatment or during acute exposure. We conclude that chronic amiodarone treatment reduces overall Na⁺-K⁺ pump capacity in cardiac ventricular myocytes. In contrast, acute exposure of myocytes to amiodarone reduces the apparent Na⁺ affinity of the Na⁺-K⁺ pump. An amiodarone-induced inhibition of the hyperpolarizing Na⁺-K⁺ pump current may contribute to the action potential prolongation observed during treatment with this drug.