Block of Na channels in the membrane of myelinated nerve by benzocaine

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Abstract
The actions of the neutral local anesthetic benzocaine on Na channels were studied in voltage-clamp experiments on single myelinated nerve fibres of the frog by measurement of sodium currents, asymmetry currents, and sodium current fluctuations. 1 mM benzocaine reduced the peak Na currents during various depolarizationsV between 20 and 120 mV to 63% of their control values but did not change the time constant of Na activation. 1 mM benzocaine altered the asymmetry currents during 1 ms pulsesV between 20 and 120 mV in the same way as the early Na currents: It reduced the amplitude to 64% but did not affect the kinetics of the currents. The charge displacement of the asymmetry current during the pulse (Qon) was compared with the charge displacement after the pulse (Qoff). Without benzocaine the relative chargeQoff/Qon declined to a constant level (0.42 atV=40 mV, 0.25 atV=100 mV) with increasing pulse durations. In the presence of 1 mM benzocaine the chargesQoff after pulses toV=40 or 100 mV are almost independent of pulse duration and approximately equal to the controlQoff values after 5.6 ms pulses. Thus, the immobilizations caused by Na inactivation and benzocaine are not additive. Na currents and Na-current fluctuations were recorded during depolarizationsV between 24 and 48 mV in the presence of 0.1 mM benzocaine and 7 μMAnemonia toxin II. A lower limit of 8.6 pS was derived for the conductance of a single Na channel. The value agrees with other estimates of the conductance of Na channels which had not been treated by local anesthetics. This suggests an “all-or-none blocking” of Na channels by benzocaine.