Rhythmic automatic depolarizations (RAD) were produced in guinea-pig papillary muscles depolarized to membrane potentials at which depolarizations depend on membrane currents passing through the slow channel. Verapamil depressed the RAD and decreased their overshoot. These verapamil effects were dependent on its concentration either in the bath (in vitro) or in plasma and myocardium (in vivo). Increase in [Ca++] counteracted the effects of verapamil on RAD. Lidocaine concentrations ranging from 4 to 16 mg/l had no effect on overshoot and only a slight effect on the rate of RAD. We conclude that RAD are more sensitive to nonlethal and presumably therapeutic concentrations of verapamil than to high, presumably toxic, concentrations of lidocaine.
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