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 outside-out 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.
Grudt
T J
TJ
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Jahr
C E
CE
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D004558:Electric Stimulation; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D016202:N-Methylaspartate; D009431:Neural Conduction / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D007211:Indoles; D009467:Neuromuscular Depolarizing Agents; D010069:Oxadiazoles; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; C063768:5-fluoroindole-2-carboxylic acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D005998:Glycine