Quisqualate activates N-methyl-D-aspartate receptor channels in hippocampal neurons maintained in culture

Whole-cell and single-channel patch-clamp recordings from hippocampal neurons in culture have been used to study the receptor channel selectivity of the glutamate analog quisqualate. The dose-response relationship of quisqualate acting at the N-methyl-D-aspartate (NMDA) receptor was measured as that portion of the whole-cell current activated by quisqualate that could be blocked by the addition of two NMDA antagonists, 5-fluoroindole-2-carboxylic acid, a competitive antagonist of the NMDA receptor-associated glycine site, and D-2-amino-5-phosphonovalerate, a competitive NMDA binding site antagonist. We found that quisqualate was 10-fold less potent than NMDA. In outsideout patches quisqualate activates single-channel events that range in conductance from 5 to 50 pS. The NMDA antagonists 5-fluoroindole-2-carboxylic acid and D-2-amino-5-phosphonovalerate completely blocked all of the 40-50-pS channel openings in the presence of quisqualate. These results indicate that quisqualate gates 40-50-pS events by activating NMDA receptor channels.