Cyclopiazonic acid exerts negative inotropic effects on adult rat myocardium, likely through inhibition of sarcoplasmic reticulum function, while sparing neonatal myocardium.
May indicate age-dependent SR maturation in rat myocardium; hypothesis-generating for developmental cardiac pharmacology without clinical translation.
Cyclopiazonic acid (CPA), a mycotoxin from Aspergillus and Penicillium, has been described as a highly selective inhibitor of Ca(2+)-ATPase in the sarcoplasmic reticulum (SR) in skeletal and smooth muscles but no reports at present deal with the effect of CPA in cardiac muscle. In the present study, we examined the inotropic effect of CPA on adult and neonatal rat myocardia, the contractions of which are known to be highly dependent on Ca(2+)-release from the sarcoplasmic reticulum and transsarcolemmal Ca(2+)-influx, respectively. CPA (30 microM) produced a negative inotropic effect in adult preparations, accompanied by marked prolongation of the contraction duration. In contrast, CPA had minimum effects on neonatal myocardium. Thus we have demonstrated that CPA exerts negative inotropic effects on adult myocardium probably through inhibition of SR function.
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Agata et al. (1993) studied this question.
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