The present experiments were performed to study the actions of cyclopiazonic acid on triggered activities generated in vitro in ventricular papillary muscle and cardiomyocytes isolated from the hearts of healthy male Syrian hamsters (Biobreeders F1B). Action potentials (APs) of ventricular muscle with a diameter around 1.5 mm were recorded using a microelectrode technique and force was recorded using a transducer. Ventricular preparations were driven at 2 Hz in high [Ca]o (9 mM)-low [K]o (1 mM) solution to induce delayed after depolarizations (DADs). Triggered activities were induced on resumption of electrical stimulation after a rest period of 20 sec. Effects of cyclopiazonic acid (3-10 microM) on steady-state rhythms and post-rest triggered activities were determined. Results revealed that cyclopiazonic acid initially enhanced the amplitude of DADs and induced post-rest triggered rhythms. However, after several minutes of cyclopiazonic acid exposure, AP duration (APD) was prolonged and DADs were significantly depressed. The effects on APD and DADs were reversible after washout of cyclopiazonic acid, but the diastolic potential during rest period oscillated and was able to generate high-frequency spontaneous APs at a reduced potential level. In ventricular myocytes isolated enzymatically, ionic currents were measured using of whole-cell patch-clamp techniques. In a high [Ca]o-low [K]o solution, a series of oscillatory transient inward currents (I(ti)) were obtained on repolarization to the holding potential (-45 mV) after a depolarizing pulse to the test potential of +20 mV for 1.2 sec. Cyclopiazonic acid (10 microM) reduced significantly the magnitude of I(ti). The present results in hamster ventricular cells suggested that cyclopiazonic acid by inhibiting the sarcoplasmic reticulum (SR)-Ca2+ pump would gradually deplete the amount of Ca2+ within the SR. The consequent reduction in the amount of Ca2+ released into the cytoplasm by cyclopiazonic acid might inhibit triggered arrhythmia through a reduction of DADs and I(ti).