Effect of verapamil and D 600 on cardiac transmembrane potentials

The effects of verapamil and D 600 on the transmembrane potential of guinea pig and cat left auricles were analysed using KC1 filled intracellular microelectrodes. Verapamil (2 microgram/ml) seemed to have no considerable effect on resting potential (RP) and on the maximum depolarization rate (Vmax) of the electrically driven guinea pig auricle. This was the case when transmembrane potential measurements performed for an hour were averaged. If the data were evaluated in relation to time, a clear-cut biphasic effect of verapamil became obvious: in the period from 10 to 30 min after verapamil application a significant (5%) increase of RP and of Vmax (26%) could be seen; these changes became progressively slighter during the period from 30 to 50 min after verapamil application, while in the third phase (50 to 70 min) a significant decrease of both RP (11%) AND Vmax (27%) occurred in the guinea pig auricle. Similar kinetics of the verapamil effect were observed in the cat auricle. Verapamil at higher (3 microgram/ml) concentration decreased RP and Vmax. The time dependent dual effect of verapamil is probably unrelated to the inhibition of Ca conductivity as D 600, a more effective inhibitor in a corresponding dose (0.5 microgram/ml), failed to produce this type of time-dependent effect. A fourfold increase of Ca2+ concentration prevented the delayed depressing effect of 2 microgram/ml verapamil, but did not influence its early stimulating effect.