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

Abstract

• 1. 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.

• 2. 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.

• 3. 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.

• 4. The charge displacement of the asymmetry current during the pulse (Q _on) was compared with the charge displacement after the pulse (Q _off). Without benzocaine the relative chargeQ _off/Q _on 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 chargesQ _off after pulses toV=40 or 100 mV are almost independent of pulse duration and approximately equal to the controlQ _off values after 5.6 ms pulses. Thus, the immobilizations caused by Na inactivation and benzocaine are not additive.

• 5. 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.