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 microM) 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 alpha-difluoromethylornithine, an inhibitor of polyamine synthesis, did not modify cellular responses to isoproterenol (10(-9)-10(-7) M). beta-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.
Ventura
C
C
Institute of Biochemistry A. Bonsignore, University of Sassari, Italy.
Ferroni
C
C
Flamigni
F
F
Stefanelli
C
C
Capogrossi
M C
MC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002469:Cell Separation; D000518:Eflornithine / Q000494:pharmacology; D004558:Electric Stimulation; D006352:Heart Ventricles; D006706:Homeostasis / Q000187:drug effects*; D007425:Intracellular Membranes / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D011073:Polyamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D011073:Polyamines; D007545:Isoproterenol; D002118:Calcium; D000518:Eflornithine