Quisqualate-induced changes in extracellular sodium and calcium concentrations persist in the combined presence of NMDA and non-NMDA receptor antagonists in rat hippocampal slices.

In the CA1 stratum pyramidale of rat hippocampal slices we have used Ca2(+)- and Na(+)-sensitive microelectrodes to measure the changes in [Ca2+]o, [Na+]o and associated slow field potentials elicited by the iontophoretic application of the excitatory amino acids N-methyl-D-aspartic acid (NMDA), quisqualic acid (Quis), alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) and glutamic acid (Glu) in the presence of the NMDA receptor antagonists 2-amino-5-phosphonovaleric acid (AP5) and ketamine and the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Although a combination of these antagonists blocked stimulation-induced synaptic field potentials as well as AMPA- and NMDA-induced ionic changes and associated field potentials, Quis-induced ionic changes and associated field potentials could still be observed after 60 min. These residual Quis signals were also resistant to 2-amino-3-phosphonopropionic acid (AP3) and 2-amino-4-phosphonobutyric acid (AP4) suggesting that metabotropic receptors do not play a role in the generation of these signals. We suggest that the receptor class activated under these conditions may play a role in CNQX/AP5-resistant epileptogenesis as well as other pathophysiological conditions.