Inhibitors of high-affinity uptake augment depolarizations of hippocampal neurons induced by glutamate, kainate and related compounds.

Actions of dihydrokainate (DHKA) and 3-hydroxy-DL-aspartate (HAsp), inhibitors of high-affinity uptake for L-glutamate (Glu), were studied in vitro in thin hippocampal slices of the guinea pig. The amplitude of the depolarizations induced by Glu and by L-aspartate (Asp) in CA3 neurons are markedly augmented by DHKA and HAsp. Depolarizations induced by D-homocysteate (DH) were unaffected by the inhibitors. In about half of the neurons, depolarizations induced by L-homocysteate (LH) and by quisqualate (Quis) were slightly augmented by the inhibitors. Fast responses to kainate (KA) were augmented by the inhibitors to a similar extent as were Glu responses whereas slow KA responses were insensitive to HAsp. HAsp was without effect on excitatory postsynaptic potentials elicited by stimulation of granular layer. These findings are in general agreement with the biochemical data on amino acid uptake processes and are also consistent with the slow time-courses of depolarizations induced by DH, LH and Quis. Augmentation of fast KA responses provides strong evidence for the hypothesis that an KA pulse causes a liberation of Glu and/or Asp from the tissue and the liberated amino acid(s) induces the fast KA response in neurons nearby.