Effects of 2,3-butanedione monoxime on sarcoplasmic reticulum of saponin-treated rat cardiac muscle.

We have studied the effects of 2,3-butanedione monoxime (BDM) on the sarcoplasmic reticulum (SR) of saponin-treated rat cardiac trabeculae. Rapid application of 20 mM caffeine released Ca2+ from the SR, which was detected using the fluorescent Ca2+ indicator indo 1. The amplitude of the caffeine-induced Ca2+ transient was used as an index of the Ca2+ content of the SR before, during, and after exposure to various concentrations of BDM. BDM (1-5 mM) had little effect on caffeine-induced Ca2+ release. At these levels of BDM, force was inhibited predominantly by a direct action of BDM on the myofilaments. However, with higher concentrations (5-30 mM), BDM caused a concentration-dependent decrease in the amount of Ca2+ released from the SR in response to caffeine. This action of BDM may contribute to the negative inotropic effect of the drug in intact cardiac preparations by reducing the amount of Ca2+ available for release during systole. Rapid application of BDM induced a net release of Ca2+ from the SR. Both BDM and caffeine-induced Ca2+ releases were abolished following treatment of the muscle with 10 microM ryanodine. BDM failed to release Ca2+ in the absence of ATP or after substitution of ATP with nonhydrolyzable adenine nucleotides. In contrast, caffeine released Ca2+ in the absence of ATP. The possible involvement of the Ca(2+)-uptake pump in the action of BDM on the SR is discussed.