Effects of local anesthetic QX-314 on the membrane properties of hippocampal pyramidal neurons.
The quaternary lidocaine derivative QX-314 was applied internally to CA1 pyramidal neurons of the guinea-pig hippocampal slice preparation. This local anesthetic blocked both fast, Na+-dependent action potentials and the voltage-dependent, non-inactivating Na+ conductance. Partially blocked Na+ spikes exhibited pronounced frequency-dependent depression at rates as low as 0.2 Hz. Ca++-dependent electrogenesis, synaptic potentials and glutamate-induced depolarizations were apparently unaffected even after large doses of QX-314. The results indicate that the cellular mechanisms of local anesthetics on central neuronal membranes are similar to those described for peripheral axons. The frequency-dependence of spike blockade may account for some of the effects of local anesthetics on the central nervous system in vivo. Additionally, the localized intracellular application of QX-314 may prove useful as a specific pharmacological tool in studies of central neurons.
D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008566:Membranes / Q000187:drug effects; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects*; D011712:Pyramidal Tracts / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; C012647:QX-314; D013779:Tetrodotoxin; D008012:Lidocaine