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 mu M CPA concentration-dependentl y decreased the contractile force and prolonged the relaxation phase o f twitch contractions. In skinned papillary muscle with functional sar coplasmic reticulum (SR) preserved, application of CPA during the Ca+ loading period reduced the peak tension of subsequent caffeine-induce d contractions. When CPA was applied during exposure to caffeine, it h ad 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 S R. CPA had no substantial influence on tile peak inward and steady-sta te membrane currents of isolated myocardial cells. These results sugge st that CPA inhibits Ca uptake into SR by acting as a specific inhibit or of SR Ca++-ATPase in cardiac muscle as in skeletal and smooth muscl es and thus provides a valuable pharmacological tool for studying myoc ardial excitation-contraction mechanisms.