Abstract
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.
Footnotes
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Send reprint requests to: Dr. David Whalley, Cardiology Department, Royal North Shore Hospital, Pacific Highway, St. Leonards, 2065, Sydney, Australia.
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↵1 This study was supported by the National Heart Foundation of Australia (Grant 94S4055) and by the North Shore Heart Research Foundation.
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↵2 D.F.G. was the recipient of a National Health and Medical Research Council of Australia Medical Postgraduate Research Scholarship.
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↵3 P.S.H. was the recipient of a Postgraduate Medical Research Scholarship from the National Heart Foundation of Australia.
- Abbreviations:
- Ip
- Na+-K+pump current
- QTc
- corrected QT interval
- T4
- thyroxine
- T3
- triiodothyronine
- HEPES
- N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid
- EGTA
- ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid
- TMA
- tetramethylammonium
- aiNa
- intracellular Na+ activity
- [Na]pip
- pipette Na+ concentration
- [K]o
- extracellular K+ concentration
- K0.5
- concentration for half-maximal pump activation
- Vm
- membrane potential
- Ip-Vm
- pump current-voltage relationship
- Received April 1, 1997.
- Accepted September 16, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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