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.
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - Jan 1998|