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 and indicated that the cellular mechanisms of local anesthetics on central neuronal membranes are similar to those described for peripheral axons.

Abstract

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.