Adenosine reduces the Ca2+ transients of isoproterenol-stimulated rat ventricular myocytes
Department of Physiology
Adenosine; Animals; Calcium; Cells, Cultured; Fluorescence; Fura-2; Heart Ventricles; Isoproterenol; Male; Myocardium; Phenylisopropyladenosine; Rats; Rats, Inbred Strains; Xanthines
Cardiovascular Diseases | Cellular and Molecular Physiology | Physiology
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.
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Citation: Am J Physiol. 1991 Dec;261(6 Pt 1):C1107-14.