TY - JOUR T1 - Amiodarone Inhibits the Na<sup>+</sup>-K<sup>+</sup> Pump in Rabbit Cardiac Myocytes after Acute and Chronic Treatment JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 75 LP - 82 VL - 284 IS - 1 AU - David F. Gray AU - Anastasia S. Mihailidou AU - Peter S. Hansen AU - Kerrie A. Buhagiar AU - Nerida L. Bewick AU - Helge H. Rasmussen AU - David W. Whalley Y1 - 1998/01/01 UR - http://jpet.aspetjournals.org/content/284/1/75.abstract N2 - 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 (Ip) using the whole-cell patch-clamp technique in single ventricular myocytes isolated from rabbits. Chronic treatment with oral amiodarone for 4 weeks reduced Ip 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 Ipwhen patch pipettes contained 10 mM Na+ but had no effect on Ip 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. The American Society for Pharmacology and Experimental Therapeutics ER -