The quaking mouse: an epileptic mutant with alterations affecting the modulatory mechanisms of the NMDA receptor complex.
The binding of [3H]glutamate and of [3H]1-(1-(2-thienyl)cyclohexyl)piperidine [( 3H]TCP) has been examined in the genetically epileptic mutant mouse, quaking. The density of [3H]glutamate binding sites did not differ between the quaking mice and their controls of the same strain. In the absence of exogenous glutamate or glycine, the density of [3H]TCP binding sites was also similar in the two strains. In both the mutants and their controls, exogenously added glutamate, glycine and glutamate plus glycine dose-dependently increased the binding of [3H]TCP. In the 3 conditions, the modulation of [3H]TCP binding was significantly more efficient in the quaking mice than in the controls. Furthermore, in the presence of glutamate (10(-5) M), the increase of the affinity of the ligand for the ion channel binding site was higher in the mutants than in the controls. These results suggest that the modulatory mechanisms of the N-methyl-D-aspartate/ionophore receptor complex might be altered in these mutants. These alterations might be related to the previously observed anticonvulsant properties of NMDA receptor antagonists in the quaking mouse model of inherited epilepsy.
Mitrovic
N
N
Laboratoire de Neurochimie-Anatomie, C.N.R.S.-U.P.M.C., Paris, France.
Caboche
J
J
Carré
J B
JB
Besson
M J
MJ
Maurin
Y
Y
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004827:Epilepsy / Q000235:genetics / Q000503:physiopathology*; D005971:Glutamates / Q000378:metabolism / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008821:Mice, Quaking; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism* / Q000502:physiology
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; C012058:tenocyclidine; D010622:Phencyclidine; D005998:Glycine