Frequency-dependence of neuromuscular blockade in the presence of d-tubocurarine.

The frequency-dependence of neuromuscular blockade in the presence of d-tubocurarine (dTC) was studied in the vascular perfused rat phrenic nerve-hemidiaphragm preparation by intracellular recording. Endplate potential (EPP) amplitude decreased as the frequency of stimulation increased (2.5-40 Hz). Additionally, the slopes of the regression lines of EPP amplitude versus the log of stimulation frequency decreased when the dTC concentration was increased. Since the dependence of neuromuscular blockade on frequency was not enhanced by higher concentrations of dTC, the postjunctional channel-blocking hypothesis does not sufficiently explain frequency-dependent neuromuscular blockade in the presence of dTC. However, the present results are compatible with the hypothesis that dTC influences neuromuscular blockade via a prejunctional action, affecting acetylcholine release.