Adenosine reduces the Ca2+ transients of isoproterenol-stimulated rat ventricular myocytes.
Adenosine in the heart attenuates the contractile and metabolic effects of beta-adrenergic stimulation. The effect of adenosine on changes in intracellular Ca2+ concentration [( Ca2+]i) elicited with electrical stimulation was studied in rat ventricular myocytes in the absence and presence of isoproterenol (ISO). Fura-2 was utilized as a Ca2+ indicator. Autofluorescence was determined, and in vivo calibration was conducted, for each myocyte. Phenylisopropyladenosine (PIA; 10(-7) M; 5 min), an adenosine A1 receptor agonist, had no effect on the Ca2+ transient magnitude (TM) or the rate of Ca2+ transient decline determined at 150 nM Ca2+(i) (RD150). ISO (10(-8) M; 1 min) in the continued presence of PIA resulted in a 16% increase in the TM, but no change in the RD150. Inhibiting the PIA with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 10(-7) M; 3 min) in the continued presence of ISO plus PIA resulted in a further 51% increase in the TM and a 57% increase in the RD150. In PIA-treated myocytes, ISO-induced spontaneous high-frequency Ca2+ transients occasionally were observed after the inhibition of PIA by DPCPX. The results of this study suggest that adenosine attenuates myocardial contractile responses to beta-adrenergic stimulation, in part, by reducing the beta-adrenergic-induced changes in the Ca2+ transients occurring in the contracting ventricular myocyte.
Fenton
R A
RA
Department of Physiology, University of Massachusetts Medical School, Worcester 01655.
Moore
E D
ED
Fay
F S
FS
Dobson
J G
JG
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005453:Fluorescence; D016257:Fura-2; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; D010660:Phenylisopropyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D007545:Isoproterenol; D002118:Calcium; D016257:Fura-2