Pharmacological isolation and characterization of NMDA receptor-mediated synaptic potential in the dentate gyrus of rat hippocampal slices.
We attempted to observe the dentate gyrus field potential evoked by low-frequency stimulation of the perforant path in Mg(2+)-free medium and identify the N-methyl-D-aspartate (NMDA) receptor-mediated synaptic potential using rat hippocampal slices. When perfusing solution was changed from normal medium (1.3 mM Mg2+) to Mg(2+)-free medium, the evoked potential was greatly increased and secondary population spikes appeared following a primary population spike. The evoked potential recorded in Mg(2+)-free medium was only partly blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist. The CNQX-resistant component of the evoked potential in Mg(2+)-free medium was completely abolished by 30 microM DL-2-amino-5-phosphonovalerate, a NMDA receptor antagonist, indicating that the NMDA receptor-mediated synaptic response can be isolated by masking the non-NMDA receptor-mediated component of the evoked potential under the Mg(2+)-free condition. The isolated NMDA receptor-mediated synaptic potential was also blocked by 7-chlorokynurenate, an antagonist at the glycine site of the NMDA receptor, and restored by the concomitant presence of glycine. Observation of pharmacologically isolated NMDA receptor-mediated synaptic potential is a simple and good method for studying the direct effects of drugs on NMDA receptor-mediated responses.
Abe
K
K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Saito
H
H
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid; D008274:Magnesium; C057013:7-chlorokynurenic acid; D005998:Glycine