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-ICl) more potently (to 46% of the control value) than the gamma-aminobutyric acid-induced Cl- current (GABA-ICl; to 75%), whereas the agent had little effect on the excitatory glutamate response. The reduction in the Gly-ICl was dose-dependent, with a dissociation constant (KD) 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-ICl. Benzocaine, a neutral local anesthetic at physiological pH, decreased the Gly-ICl 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-ICl. The depression of the Gly-ICl and GABA-ICl in central neurons may contribute to local anesthetic-induced convulsions.
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D004213:Dissociative Disorders; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000779:Anesthetics, Local; D018377:Neurotransmitter Agents; D008012:Lidocaine; D005998:Glycine