Amiodarone inhibits the Na(+)-K+ pump in rabbit cardiac myocytes after acute and chronic treatment.
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 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.
Gray
D F
DF
Cardiology Department, Royal North Shore Hospital, St. Leonards, NSW, Australia.
Mihailidou
A S
AS
Hansen
P S
PS
Buhagiar
K A
KA
Bewick
N L
NL
Rasmussen
H H
HH
Whalley
D W
DW
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D004562:Electrocardiography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013961:Thyroid Gland / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D000638:Amiodarone; D011188:Potassium