title: N-methyl-D-aspartate receptor plasticity in kindling: quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex.
abstract: Kindling is an animal model of epilepsy and neuronal plasticity produced by periodic electrical stimulation of the brain. Electrophysiologic studies indicate that this phenomenon is associated with increased participation of N-methyl-D-aspartate (NMDA) receptors in excitatory synaptic transmission. Biochemical studies suggest that a change intrinsic to the NMDA receptor-channel complex may contribute to the increase in NMDA receptor-mediated synaptic transmission. We tested this idea by measuring the binding of 3-[(+)-2-(carboxypiperazin-4-yl)][1,2-3H]propyl-1-phosphonic acid ([3H]CPP), [3H]glycine, and tritiated N-[(1-thienyl)cyclohexyl]piperidine [( 3H]TCP) to rat hippocampal membranes. In this preparation these ligands are selective for the NMDA receptor, the strychnine-insensitive glycine receptor, and the NMDA receptor-gated ion channel, respectively. Kindling increased the density of CPP, glycine, and TCP binding sites in hippocampal membranes by 47%, 42%, and 25%, respectively. No significant changes were detected in the affinity of these binding sites. Surprisingly, alterations in the glycine binding site were detected in animals sacrificed 1 month but not 1 day after the final kindling stimulation. Thus, delayed upregulation of the NMDA receptor-channel complex may be one molecular mechanism that maintains the long-lasting hyperexcitability of hippocampal neurons in kindled animals.
authors: Department of Pharmacology, Duke University Medical Center, Durham, NC.
authors: G C
authors: GC
authors: Yeh
authors: D W
authors: DW
authors: Bonhaus
authors: J V
authors: JV
authors: Nadler
authors: J O
authors: JO
authors: McNamara
mesh_terms: D000818:Animals; D003292:Convulsants / Q000378:metabolism; D004558:Electric Stimulation; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology* / Q000503:physiopathology; D013287:Illicit Drugs; D007473:Ion Channels / Q000502:physiology*; D007696:Kindling, Neurologic; D008297:Male; D009473:Neuronal Plasticity; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology
chemical_list: D003292:Convulsants; D013287:Illicit Drugs; D007473:Ion Channels; D010879:Piperazines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C012058:tenocyclidine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D010622:Phencyclidine; D005998:Glycine