Differences in frequency dependence of quinidine effects on force, dV/dtmax and action potential duration

In the left atria of the guinea-pig heart, quinidine produces a transient inotropic effect that is largest at low rates of stimulation; at high rates, the negative inotropic action of quinidine prevails. In contrast to the depression of the maximum rate of depolarization (dV/dtmax), the quinidine-induced prolongation in action potential duration was largest at low rates of stimulation. Recovery from block during rest was observed only for dV/dtmax; the prolongation in action potential duration, however, did not reverse but became most prominent after rest. The differences in frequency dependence of quinidine-induced decrease in dV/dtmax and prolongation of action potential duration can be explained if the drug interacts preferentially with the sodium channels while they are in an open or inactivated state, but with potassium channels while they are closed.