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.