LOCAL-ANESTHETICS REDUCE THE INHIBITORY NEUROTRANSMITTER-INDUCED CURRENT IN DISSOCIATED HIPPOCAMPAL-NEURONS OF THE RAT

The effects of local anesthetics on amino acid-induced currents were examined using the whole-cell configuration of the patch clamp technique in dissociated hippocampal pyramidal neurons of the rat. Lidocaine (3 mM) decreased the glycine-induced Cl- current (Gly-I-Cl) more potently (to 46% of the control value) than the gamma-aminobutyric acid-induced Cl- current (GABA-I-Cl; to 75%), whereas the agent had little effect on the excitatory glutamate response. The reduction in the Gly-I-Cl was dose-dependent, with a dissociation constant (K-D) of 3 mM and a Hill coefficient of 0.96. A non-competitive inhibition was suggested by a double reciprocal plot of the effects of lidocaine on the concentration-response curve of the Gly-I-Cl. Benzocaine, a neutral local anesthetic at physiological pH, decreased the Gly-I-Cl more potently than lidocaine, while QX314, a permanently charged quaternary derivative of lidocaine, produced a much smaller inhibition, thereby indicating that the neutral form of local anesthetics is more effective in reducing the Gly-I-Cl. The depression of the Gly-I-Cl and GABA-I-Cl in central neurons may contribute to local anesthetic-induced convulsions.