Hwang HR, Shen YF, Chen YC, Liu CP, Lin CI.Effects of
cyclopiazonic acid on triggered activities in ventricular muscle
and cardiomyocytes isolated from hamster hearts.
Chin J Physiol. 2004 Sep 30;47(3):137-42.
Section of Cardiology, Department of Medicine, Veterans
General Hospital-Kaohsiung, Kaohsiung 813, Taiwan, ROC.
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).
PMID: 15612531
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