Changes in voltage activation of contraction in frog skeletal muscle fibres as a result of sarcoplasmic reticulum Ca2+-ATPase activity

The effects of cyclopiazonic acid, a specific sarcoplasmic reticulum Ca2+-A TPase inhibitor, on isometric tension were studied in response to prolonged steady-state depolarization induced by a rapid change in extracellular pot assium concentration (potassium contractures) in frog semitendinosus muscle fibres. Cyclopiazonic acid (1-10 mu M) enhanced the amplitude and time-cou rse of relaxation of 146 mM potassium contracture. In the presence of cyclo piazonic acid 0.5 mu M, the relationship between the amplitude of potassium contractures and the membrane potential shifted to more negative potential s, whereas the steady-state inactivation curve was unchanged. These observa tions suggest that cyclopiazonic acid has no effect on voltage sensors. The difference between potassium contractures in the absence and presence of c yclopiazonic acid in skeletal muscle fibres implies that the amplitude and slow relaxation of tension during prolonged steady-state depolarization may be expected to depend not only on inactivation of the process regulating c alcium release from the sarcoplasmic reticulum but also on the ability of t he sarcoplasmic reticulum to pump calcium.