Abstract
Involvement of the Na+/Ca2+ exchanger in ouabain-induced inotropy and arrhythmogenesis was examined with a specific inhibitor, SEA0400. In right ventricular papillary muscle isolated from guinea-pig ventricle, 1 microM SEA0400, which specifically inhibits the Na+/Ca2+ exchanger by 80%, reduced the ouabain (1 microM)-induced positive inotropy by 40%, but had no effect on the inotropy induced by 100 microM isobutyl methylxantine. SEA0400 significantly inhibited the contracture induced by low Na+ solution. In HEK293 cells expressing the Na+/Ca2+ exchanger, 1 microM ouabain induced an increase in intracellular Ca2+, which was inhibited by SEA0400. The arrhythmic contractions induced by 3 microM ouabain were significantly reduced by SEA0400. These results provide pharmacological evidence that the Na+/Ca2+ exchanger is involved in ouabain-induced inotropy and arrhythmogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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Aniline Compounds / pharmacology*
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Animals
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Anti-Arrhythmia Agents / pharmacology*
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Arrhythmias, Cardiac / chemically induced
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Arrhythmias, Cardiac / physiopathology*
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Calcium / metabolism
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Cardiotonic Agents / pharmacology*
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Cell Line
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Cytoplasm / drug effects
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Cytoplasm / metabolism
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Enzyme Inhibitors / pharmacology*
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Guinea Pigs
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In Vitro Techniques
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Myocardial Contraction / drug effects
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Ouabain / pharmacology*
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Papillary Muscles
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Phenyl Ethers / pharmacology*
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Phosphodiesterase Inhibitors / pharmacology
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Sodium-Calcium Exchanger / antagonists & inhibitors*
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Sodium-Calcium Exchanger / physiology*
Substances
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Aniline Compounds
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Anti-Arrhythmia Agents
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Cardiotonic Agents
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Enzyme Inhibitors
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Phenyl Ethers
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Phosphodiesterase Inhibitors
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SEA 0400
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Sodium-Calcium Exchanger
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Ouabain
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Calcium
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1-Methyl-3-isobutylxanthine