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.
Mudrick
L A
LA
Institut für Neurophysiologie, Universität zu Köln, Cologne, F.R.G.
Heinemann
U
U
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005071:Evoked Potentials / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D007051:Ibotenic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D007649:Ketamine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D012964:Sodium; D002118:Calcium