RT Journal Article
SR Electronic
T1 Amiodarone Inhibits the Na+-K+ Pump in Rabbit Cardiac Myocytes after Acute and Chronic Treatment
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 75
OP 82
VO 284
IS 1
A1 David F. Gray
A1 Anastasia S. Mihailidou
A1 Peter S. Hansen
A1 Kerrie A. Buhagiar
A1 Nerida L. Bewick
A1 Helge H. Rasmussen
A1 David W. Whalley
YR 1998
UL http://jpet.aspetjournals.org/content/284/1/75.abstract
AB 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