AMIODARONE INHIBITS THE NA-K+ PUMP IN RABBIT CARDIAC MYOCYTES AFTER ACUTE AND CHRONIC TREATMENT()

Amiodarone has been shown to affect cell membrane physicochemical prop erties, 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 isola ted from rabbits. Chronic treatment with oral amiodarone for 4 weeks r educed I-p when myocytes were dialyzed with patch-pipettes containing either 10 mM Na+ or 80 mM Na+. In myocytes from untreated rabbits, acu te exposure to amiodarone in vitro reduced I-p when patch pipettes con tained 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 th e pump for extracellular K+ either after chronic treatment or during a cute exposure. We conclude that chronic amiodarone treatment reduces o verall Na+-K+ pump capacity in cardiac ventricular myocytes. In contra st, acute exposure of myocytes to amiodarone reduces the apparent Naaffinity of the Na+-K+ pump. An amiodarone-induced inhibition of the h yperpolarizing Na+-K+ pump current may contribute to the action potent ial prolongation observed during treatment with this drug.