[Effects of ouabain, caffeine, and diltiazem, on spontaneous cyclic Ca2+ release from sarcoplasmic reticulum in the skinned papillary muscles of guinea pigs].

The aim of this study was to assess whether ouabain has a direct action on the sarcoplasmic reticulum (SR) sufficient to be responsible for the mechanism of the inotropic action, and whether caffeine and diltiazem, which inhibit ouabain-induced afterpotential and after-contraction, can inhibit the effects of ouabain on the SR. As one of the functions of SR, spontaneous cyclic contractions (cyclic Ca2+ release from the SR) in saponin-treated skinned fibers of guinea pig papillary muscles were used. Ouabain 10(-9)-10(-7) M increased the frequency of cyclic contractions and induced an incomplete muscle relaxation. Caffeine 1-5 mM and diltiazem 1-5 mM induced a sustained tension. In the fibers treated with ouabain, caffeine and diltiazem induced a sustained tension. In Brij-58 treated skinned fibers, 10(-9) M ouabain did not change the Ca2+ sensitivity of the contractile system. It is now known that ouabain increases intracellular calcium transients. An incomplete muscle relaxation of cyclic contractions seems to be due to both increased SR Ca2+ release and decreased Ca2+ reuptake by SR. Thus, we suppose that ouabain-induced increase in intracellular calcium transients is due to increased intracellular Ca2+, which may be one of the mechanisms in the inotropic action. The masking effects of caffeine and diltiazem on the ouabain-induced increase in cyclic contractions seem to be responsible for the inhibitory effects of drugs on digitalis-induced afterpotential and after contraction.