EFFECTS OF COMPOUND-48/80 ON THE CA-2+ RELEASE BY REVERSAL OF THE CA-2+ PUMP AND BY THE CA-2+ CHANNEL OF SARCOPLASMIC-RETICULUM MEMBRANES

The effect of the calmodulin antagonist, compound 48 80, on the Ca2+ release from skeletal muscle sarcoplasmic reticulum was investigated. Both the Ca2+ release by reversal of the Ca2+ pump and the Ca2+ release by the Mg2+-controlled Ca2+ channel were studied. It was observed that, when reversal of the pump is inoperative and Mg2+ is not present in the reaction medium, 48 80 stimulates Ca2+ release from the vesicles. In contrast, in the presence of Mg2+, which blocks the Ca2+ channel, 48 80 inhibits Ca2+ release induced by ADP and Pi. This effect is strong at low concentrations of Pi (~1 mm), whereas high concentrations (~15 mm) protect the system against the drug. Furthermore, it was observed that 48 80 has a maximum effect on the channel-mediated Ca2+ release at concentrations of about 20 μg/ml, whereas maximal inhibition of the pump-mediated Ca2+ release occurs at concentrations of about 60-80 μg/ml. The results indicate that both the Ca2+ channel complex and the Ca2+-ATPase may be target systems for the effects of 48 80 on the Ca2+ transport activity of sarcoplasmic reticulum. However, the Ca2+ channel is more sensitive to the drug, suggesting an involvement of calmodulin on this mechanism of Ca2+ release. © 1990.