Effects of cyclopiazonic acid on rat myocardium: inhibition of calcium uptake into sarcoplasmic reticulum.

The effects of cyclopiazonic acid (CPA), which is reported to inhibit Ca++ uptake into intracellular Ca++ store sites in skeletal and smooth muscles, were examined in ventricular myocardia of the adult rat. In isolated papillary muscle, 0.3 to 30 microM CPA concentration-dependently decreased the contractile force and prolonged the relaxation phase of twitch contractions. In skinned papillary muscle with functional sarcoplasmic reticulum (SR) preserved, application of CPA during the Ca++ loading period reduced the peak tension of subsequent caffeine-induced contractions. When CPA was applied during exposure to caffeine, it had no significant effect on the peak tension, but prolonged the decay of the caffeine-induced contraction. CPA had no substantial influence on the pCa-tension relationship of skinned fibers without functional SR. CPA had no substantial influence on the peak inward and steady-state membrane currents of isolated myocardial cells. These results suggest that CPA inhibits Ca uptake into SR by acting as a specific inhibitor of SR Ca(++)-ATPase in cardiac muscle as in skeletal and smooth muscles and thus provides a valuable pharmacological tool for studying myocardial excitation-contraction mechanisms.