Ketamine and phencyclidine cause a voltage-dependent block of responses to L-aspartic acid

Abstract

Excitatory amino acids depolarize central mammalian neurons by increasing membrane conductance. This increase in conductance can be voltage-dependent (i.e. N-methyl-D-aspartate or L-aspartic acid (L-ASP)) or voltage-independent (i.e. kainic acid (KA)) depending on whether or not the channel is blocked by Mg2+ [8,9]. Intracellular recordings were made from dissociated mouse spinal cord cells and conductance was calculated using constant current techniques. The dissociative anesthetics, ketamine and phencyclidine caused a selective depression in the change in conductance evoked by L-ASP but not that by KA. Under whole cell voltage-clamp (in the absence of extracellular Mg2+) this depression of responses to L-ASP was found to be highly voltage-dependent suggesting a blockade of the channel.