THE EFFECT OF QUINIDINE ON MEMBRANE ELECTRICAL ACTIVITY IN FROG AURICULAR FIBRES STUDIED BY CURRENT AND VOLTAGE CLAMP

Abstract

1 The action of quinidine sulphate 50 μm has been investigated on frog auricular trabeculae transmembrane currents recorded with a double sucrose gap apparatus. Results were obtained either in current or in voltage clamp conditions. 2 Quinidine modified the time course of repetitive activity elicited by long lasting depolarizing currents and reduced the range of current over which repetitive activity could be triggered, eventually abolishing repetitive responses altogether. 3 Several authors have emphasized the limitations of the voltage clamp method. Taking into account these limitations, the numerical values of the parameters obtained in the present work must not be considered as exact values but may be interpreted as indicators of the variations of the parameters. 4 The results are in agreement with previous findings that the main features of the action of quinidine are to produce (a) a reduced maximum rate of depolarization (MRD), (b) a reduced total amplitude of action potential, (c) a flattening of the plateau of the action potential, (d) a slight prolongation of the tail of the action potential, (e) an increased effective refractory period without greatly prolonging action potential duration, (f) no change of resting potential and of 50% repolarization time. 5 The analysis of ionic conductances has provided explanations for the above effects. 6 Quinidine reduced the reactivation kinetics of the sodium inward current, and decreased sodium conductance and the steady state of activation. These effects account for (a) and (b). 7 Quinidine increased the activation and inactivation time constants of sodium conductances, which account in part for (e). 8 Quinidine delayed reactivation of slow inward current, reduced calcium conductance, and decreased the steady state of activation of calcium conductance. These effects could account for (c). 9 The amplitudes of the two components of the delayed conductances responsible for repolarization were decreased by quinidine, and the time constant of activation for the faster of the two was slowed. These effects could account for (d) and in part for (e).