Amiodarone inhibits the Na+-K+ pump in rabbit cardiac myocytes after acute and chronic treatment

David F. Gray, Anastasia S. Mihailidou, Peter S. Hansen, Kerrie A. Buhagiar, Nerida L. Bewick, Helge H. Rasmussen, David W. Whalley*

*Corresponding author for this work

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29 Citations (Scopus)

Abstract

Amiodarone has been shown to affect cell membrane physicochemical properties, and it may produce a state of cellular hypothyroidism. Because the sarcotemmal 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(p) when 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.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume284
Issue number1
Publication statusPublished - Jan 1998
Externally publishedYes

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    Gray, D. F., Mihailidou, A. S., Hansen, P. S., Buhagiar, K. A., Bewick, N. L., Rasmussen, H. H., & Whalley, D. W. (1998). Amiodarone inhibits the Na+-K+ pump in rabbit cardiac myocytes after acute and chronic treatment. Journal of Pharmacology and Experimental Therapeutics, 284(1), 75-82.