Local anaesthetics potentiate GABA-mediated Cl- currents by inhibiting GABA uptake.

A two-electrode voltage clamp was used to examine the effects of the local anaesthetics (LAs) lidocaine, tetracaine and bupivacaine, and the meta-isomer of lidocaine (LL33), on the gamma-aminobutyric acid (GABA)-gated Cl- channel in the crayfish stretch receptor neurone. The voltage-induced current changes were recorded while exposing the neurone to GABA in saline containing different LAs. All LAs enhanced the voltage-induced Cl- current equivalent to a shift of the conductance vs GABA curve towards lower concentrations. The mechanism of the facilitation of GABA-induced conductance was found to be mainly a block of the GABA uptake in the stretch receptor neurone. Tetracaine, and to a lesser extent LL33, also seem to affect directly the GABA/receptor Cl-/channel complex resulting in an increased conductance of the channel.