Effects of papaverine on Ca++-dependent action potentials in guinea-pig myocardium depolarized by potassium

Ventricular and atrial tissues isolated from guinea-pig hearts were depolarized by exposure to 22 mM K+ to study the effects of papaverine on the Ca++-mediated slow inward current (Isi). Papaverine at 5 x 10(-6) to 5 x 10(-5) M caused a concentration-dependent decrease in the threshold current required to excite the field-stimulated tissues and an enhancement of action potential amplitude, action potential duration and maximum rate of depolarization of the Ca++-dependent action potentials. In ventricular preparations, 5 x 10(-5) and 10(-4) M papaverine invariably induced rhythmic spontaneous activity that was abolished by verapamil. It is proposed that the membranal electrical effects of papaverine in the K+-depolarized myocardium are caused by an enhancement of Isi and a decrease in K+ conductance. However, at the highest concentration studied (10(-4) M), papaverine inhibited Isi in atrial tissue, demonstrating that papaverine exerts another action on Isi opposite to that observed at lower concentrations.