The local anesthetic n-butyl-p-aminobenzoate selectively affects inactivation of fast sodium currents in cultured rat sensory neurons.

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 microM BAB on Na+ action potentials and on Na+ 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 Na+ action potentials, evoked by current pulses of increasing amplitude (current clamp) and Na+ currents, activated at different membrane potentials (voltage clamp), were investigated in the absence and presence of 100 microM BAB. The local anesthetic was applied by external perfusion for 2 or 10 min. RESULTS:In the presence of 100 microM 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,5, 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 Na+ 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 Na+ channels, but 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 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.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Van den Berg RJ,Van Soest PF,Wang Z,Grouls RJ,Korsten HH

doi

10.1097/00000542-199506000-00018

subject

Has Abstract

pub_date

1995-06-01 00:00:00

pages

1463-73

issue

6

eissn

0003-3022

issn

1528-1175

journal_volume

82

pub_type

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