Effects of lidocaine, procaine, procainamide and quinidine on electrophysiological properties of cultured embryonic chick hearts

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Abstract
The effects of lidocaine, procaine, procainamide and quinidine were studied on organ-cultured embryonic chick (2-3 day-old) ventricular cells. Lidocaine (10(-5) - 10(-4)M), in a dose-dependent manner, reduced the rate of pacemaker discharge, the action potential amplitude (APA), the maximum rate of rise (Vmax) of the upstroke of the action potential and the action potential duration at 50% repolarization (APD50). These changes occurred without alterations in the maximum diastolic potential (MDP). Extracellular electrical field stimulation could still evoke action potentials in cells arrested by 10(-4)M lidocaine, but 10(-3)M lidocaine completely abolished electrical activity. Procaine, procainamide and quinidine, at 5 X 10(-5)M to 10(-3)M, depolarized the cells to around -30 mV and reduced APA and Vmax. Procaine and procainamide increased APD50, but quinidine shortened it. All the effects described disappeared completely in about 40 min of superfusion with drug-free Tyrode solution. Isoprenaline (5 X 10(-7)M) and adrenaline (10(-6)M) restored spontaneous firing of preparations arrested by any of the antiarrhythmic agents and repolarized ventricular cells depolarized by procaine, procainamide or quinidine. Propranolol (5 X 10(-7)M) did not affect the depolarization produced by procaine (5 X 10(-4)M), but antagonized its reversal by isoprenaline. In contrast, isoprenaline (10(-6)M) did not produce recovery of automaticity of preparations arrested by verapamil (10(-5)M). Histamine (10(-5)M) or strontium (10 mM) were not able to restore rhythmic activity in cells arrested procaine. Application of long (10-15 s duration) hyperpolarizing currents did not reverse the blocking effect of procaine, procainamide and quinidine. The input resistance increased during the procaine-induced depolarization. It is suggested that the four agents studied block the slow Na+ channels responsible for the upstroke of the action potential in young chick heart cells. A drug-induced decrease in PK may occur in those cells arrested at low levels of membrane potential.