Effects of mexiletine on steady-state characteristics and recovery kinetics of V max and conduction velocity in guinea pig myocardium.

We studied the effect of the antiarrhythmic compound mexiletine on the maximal rate of rise (V max) on the action potential and on conduction velocity in isolated papillary muscles of guinea pigs. Action potentials and V max were measured by means of conventional microelectrodes. The conduction velocity was determined from extracellular recordings Mexiletine (concentrations, 4.6 x 10(-5) and 1.15 x 10(-4) mol/L) caused a depression of V max that depended on the condition examined. The h infinity curve relating V max of the action potential to the resting membrane potential was shifted along the voltage axis to more negative membrane potentials. Qualitatively equal effects were observed on the curve of membrane responsiveness relating V max to the membrane potential during the phase of repolarization of the preceding action potential. Eventually, marked prolongation of the recovery kinetics of V max by mexiletine, as well as frequency-dependent reduction of V max, could be demonstrated. The action of mexiletine on conduction velocity was very similar to its influence on V max. Thus, prolongation of the recovery kinetics was found of about the same magnitude as that measured in V max. Similarly, in experiments with K + -induced depolarizations, a dependence on the membrane potential of the action of mexiletine on the conduction velocity could be demonstrated. The results suggest that mexiletine may exert antiarrhythmic effects mainly in damaged cardiac cells exhibiting a moderately reduced resting potential.