Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes.

We investigated the effects of adenosine and isoproterenol on enzymatically dispersed ventricular myocytes from bovine and guinea pig hearts. Intracellular stimulation of relaxed myocytes with regular striation patterns and normal resting potential resulted in action potentials with full plateaus accompanied by contractions. Adenosine in concentrations up to 0.2 mM had no significant effect on any of the action potential parameters or on the basal contractility. In contrast, in the same cells, adenosine effectively antagonized the stimulatory effect of isoproterenol. Isoproterenol (1-10 nM) prolonged the action potentials by 34-41%, displaced the plateau to more positive potentials, and caused a 3-fold increase in the extent of myocyte sarcomere shortening. In the presence of adenosine (5-50 microM), isoproterenol increased the action potential duration by only 8-9%, the shift of the plateau was nearly abolished, and the increase in the extent of myocyte sarcomere shortening was less than 10%. In some of the myocytes, isoproterenol (1-10 nM) induced depolarizing afterpotentials accompanied by aftercontractions. The afterdepolarizations occasionally reached threshold resulting in triggered sustained rhythmic activity. Adenosine (20-50 microM) not only reduced the amplitude of the afterdepolarizations and aftercontractions, but also abolished the sustained rhythmic activity. We conclude, first, that isolated ventricular myocytes respond to isoproterenol and adenosine; second, that adenosine has no direct effect, but effectively antagonizes the stimulatory actions of isoproterenol; third, that findings are consistent with the ones reported for multicellular ventricular preparations; fourth, that adenosine concentrations required to attenuate the actions of isoproterenol are in the range of adenosine concentrations released by cardiac cells when oxygen availability is limited and/or demand is increased; and fifth, that endogenously released adenosine may modulate the electrophysiological and contractile effects of catecholamines.