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The Local Anesthetic n-Butyl-p-Aminobenzoate Selectively Affects Inactivation of Fast Sodium Currents in Cultured Rat Sensory Neurons

R. van den Berg,P. F. van Soest,Z. Wang,R. E. Grouls,H. Korsten

Published 1995 in Anesthesiology

ABSTRACT

Background Aqueous suspensions of the local anesthetic n-butyl-p-aminobenzoate (BAB), epidurally applied in terminal cancer patients, resulted in a sensory blockade, lasting up to several months. To investigate the mechanism of action on the cellular level, the effect of 100 micro Meter BAB on Sodium sup + action potentials and on Sodium sup + currents in dorsal root ganglion neurons from neonatal rats was studied. Methods Small neurons grown in cell culture were selected for patch-clamp measurements. Both Sodium sup + action potentials, evoked by current pulses of increasing amplitude (current clamp) and Sodium sup + currents, activated at different membrane potentials (voltage clamp), were investigated in the absence and presence of 100 micro Meter BAB. The local anesthetic was applied by external perfusion for 2 or 10 min. Results In the presence of 100 micro Meter BAB, either the firing threshold was raised or the action potential was abolished. The maximal peak conductances, underlying the fast sodium current INa,F and the slow sodium current INa,S, were not changed. However, the inactivation of INa,F Was increased by BAB. The sigmoid inactivation curve shifted 12 mV toward hyperpolarizing membrane voltages, whereas no changes were found for the inactivation of the slow Sodium sup + current. Only at short exposure times of 2 min, the effects of BAB could be reversed during a 10-min wash-out. Conclusions BAB dramatically increased the firing threshold, and in part of the sensory neurons, it blocked the action potential. The inactivation of the fast Sodium sup + channels, but not of the slow Sodium sup + channels, was increased by BAB. Thus, the block of fast Sodium sup + channels by BAB may contribute to epidural analgesia. At exposure times of 10 min, the effect of BAB was not reversible. This probably originates from its high lipid-solubility, which may be an important factor in determining the duration of the block in vivo.

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