Inhibition of nicotinic cholinoceptor mediated current in vagal motor neurons by local anesthetics.
The effects of local anesthetics on ligand-gated cation channel currents were examined in rat brainstem vagal motoneurons. Etidocaine (0.1-20 microM) blocked nicotinic cholinoceptor gated currents in cells voltage-clamped at -60 mV in a concentration-dependent manner, but at concentrations up to 100 microM did not inhibit glutamate receptor currents induced by (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), N-methyl-D-aspartate (NMDA), or glutamate. Relative to etidocaine, procaine displayed about 10-fold lower potency in antagonizing acetylcholine and its inhibitory effect, unlike that of etidocaine, was rapidly reversed by washout. Ketamine (10 microM) caused a 2-fold larger decrease in NMDA current than acetylcholine current, but did not affect AMPA current. In conclusion, (i) etidocaine and procaine possess a moderately potent blocking activity at nicotinic cholinoceptor gated channels in brainstem vagal motoneurons and (ii) in contrast with ketamine, both agents showed similar selectivity in that neither inhibited glutamate receptor gated channels at concentrations up to 0.1 mM.
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Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Bieger
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D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D005041:Etidocaine / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D014630:Vagus Nerve / Q000187:drug effects*
D000779:Anesthetics, Local; D018733:Nicotinic Antagonists; D011343:Procaine; D016202:N-Methylaspartate; D007649:Ketamine; D005041:Etidocaine