Polyamine effects on [Ca2+](i) homeostasis and contractility in isolated rat ventricular cardiomyocytes

In electrically stimulated myocytes loaded with the fluorescent Ca²⁺ indicator indo 1-acetoxymethyl ester, spermine induced a dose-dependent (100- 500 μM) negative inotropic effect, which was associated with a decrease in the magnitude of the cytosolic Ca²⁺ concentration ([Ca²⁺](i)) transient but not with changes in myofilament responsiveness to Ca²⁺. Spermidine induced a less pronounced negative inotropic effect, whereas putrescine did not modify myocyte contraction. In the unstimulated state, spermine did not alter resting [Ca²⁺](i). Superfusion of the cardiac myocytes with 10 mM α- difluoromethylornithine, an inhibitor of polyamine synthesis, did not modify cellular responses to isoproterenol (10^-9-10^-7 M). β-Adrenergic stimulation did not affect either ornithine decarboxylase activity or intracellular polyamine levels within a 10-s to 15-min period of treatment. In summary, only exogenously administered polyamines were able to influence myocyte contractility. Their negative inotropic effect resulted from changes in [Ca²⁺](i) homeostasis and required cellular depolarization.