Figure 14-8 "Use-dependent" actions of local anesthetics on excitable membrane properties. A, Ionic Na⁺ currents measured by voltage clamp are transiently activated by brief steps of depolarization applied infrequently ("tonic" test) or in a train at 10 times per second ("phasic" test, see E_m pattern in parentheses). After equilibration with 0.2 mM (0.005%) lidocaine, the currents measured tonically are reduced by about 30% from control currents. Application of the "phasic" train of depolarizations results in a dynamic reduction in currents after each depolarization, with a steady-state value of phasic inhibition reached during the train in 75% of control currents. Recovery of currents to the tonic value occurs within a few seconds when phasic testing stops (not shown). B, Action potentials are also inhibited in a phasic manner by local anesthetics. After equilibration with 0.8 mM lidocaine (0.02%), the action potential is tonically reduced by about 20% from its amplitude in drug-free solution (not shown). Stimulation by a train at 20 stimuli per second induces phasic inhibition, which further reduces the amplitude to about 30% of the control value. As with ionic currents (A), phasic inhibition of the action potential recovers rapidly when high-frequency stimulation stops.