Selective attenuation by adenosine of arrhythmogenic action of isoproterenol on ventricular myocytes

We examined whether adenosine equally attenuated the stimulatory effects of isoproterenol on arrhythmic activity and twitch shortening of guinea pig i solated ventricular myocytes. Transmembrane voltages and whole cell current s were recorded with patch electrodes, and cell twitch shortening was measu red using a video-motion detector. Isoproterenol increased the action poten tial duration at 50% repolarization (APD(50)), L-type Ca2+ current [I-Ca(L) ], and cell twitch shortening and induced delayed afterdepolarizations (DAD ), transient inward current (I-Ti), and aftercontractions. Adenosine attenu ated the arrhythmogenic actions of isoproterenol more than it attenuated th e effects of isoproterenol on APD(50), I-Ca(L), or twitch shortening. Adeno sine (0.1-100 mu mol/l) decreased the amplitude of DADs by 30 +/- 6% to 92/- 5% but attenuated isoproterenol-induced prolongation of the APD(50) by o nly 14 +/- 4% to 59 +/- 4% and had no effect on the voltage of action poten tial plateau. Adenosine (30 mu mol/l) inhibited I-Ti by 91 +/- 4% but decre ased isoproterenol-stimulated I-Ca(L) by only 30 +/- 12%. Isoproterenol-ind uced aftercontractions were abolished by adenosine (10 mu mol/l), whereas t he amplitude of twitch shortening was not reduced. The effects of adenosine on twitch shortenings and aftercontractions were mimicked by the A(1)-aden osine receptor agonist CPA (N-6-cyclopentyladenosine) and by ryanodine. In conclusion, adenosine antagonized the proarrhythmic effect of beta -adrener gic stimulation on ventricular myocytes without reducing cell twitch shorte ning.