THE LOCAL-ANESTHETIC N-BUTYL-P-AMINOBENZOATE SELECTIVELY AFFECTS INACTIVATION OF FAST SODIUM CURRENTS IN CULTURED RAT SENSORY NEURONS

Background: Aqueous suspensions of the local anesthetic n-butyl-p-amin obenzoate (BAB), epidurally applied in terminal cancer patients, resul ted in a sensory blockade, lasting up to several months. To investigat e the mechanism of action on the cellular level, the effect of 100 mu M BAB on Na+ action potentials and on Na+ currents in dorsal root gang lion neurons from neonatal rats was studied. Methods: Small neurons gr own in cell culture were selected for patch-clamp measurements. Both N a+ action potentials, evoked by current pulses of increasing amplitude (current clamp) and Na+ currents, activated at different membrane pot entials (voltage clamp), were investigated In the absence and presence of 100 mu M BAB. The local anesthetic was applied by external perfusi on for 2 or 10 min. Results In the presence of 100 mu M BAB, either th e firing threshold was raised or the action potential was abolished. T he maximal peak conductances, underlying the fast sodium current I-Na, I-F and the slow sodium current I-Na,I-S were not changed. However, th e inactivation of I-Na,I-F was increased by BAB. The sigmoid inactivat ion curve shifted 12 mV toward hyperpolarizing membrane voltages, wher eas no changes were found for the inactivation of the slow Na+ current . Only at short exposure times of 2 min, the effects of BAB could be r eversed during a 10-min wash-out. Conclusions. BAB dramatically increa sed the firing threshold, and In part of the sensory neurons, it block ed the action potential. The inactivation of the fast Na+ channels, bu t not of the slow Na+ channels, was increased by BAB, Thus, the block of fast Na+ channels by BAB may contribute to epidural analgesia. At e xposure times of 10 min, the effect of BAB was not reversible. This pr obably originates from its high lipid-solubility, which may be an impo rtant factor in determining the duration of the block in vivo.