LOCAL-ANESTHETICS POTENTIATE GABA-MEDIATED CL- CURRENTS BY INHIBITINGGABA UPTAKE

A two-electrode voltage clamp was used to examine the effects of the l ocal 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 volt age-induced current changes were recorded while exposing the neurone t o GABA in saline containing different LAs. All LAs enhanced the voltag e-induced Cl- current equivalent to a shift of the conductance us GABA curve towards lower concentrations. The mechanism of the facilitation of GABA-induced conductance was found to be mainly a block of the GAB A uptake in the stretch receptor neurone. Tetracaine, and to a lesser extent LL33, also seem to affect directly the GABA/receptor Cl-/channe l complex resulting in an increased conductance of the channel.