Biomaterial Database

Increased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons. 1998

G Stocca, and S Vicini

Department of Physiology and Biophysics, Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC 20007, USA. stoccag@medlib.georgetown.edu

1. Pharmacologically isolated miniature NMDA receptor-mediated excitatory postsynaptic currents (mN-EPSCs) were recorded in large visual cortical neurons in layer V of rat cortical slices. Haloperidol (100 microM) and CP101,606 (10 microM), two specific blockers of NMDA receptors comprising NR1/NR2B subunits, were tested on mN-EPSCs in rats at postnatal days 7 and 8 (P7-P8) and P13-P15. At both ages tested, no significant effects of these drugs were seen in the whole population of neurons, although in few neurons at both ages changes in amplitude were observed with haloperidol. Other dopamine receptor antagonists, spiperone and clozapine, failed to decrease mN-EPSCs in cortical neurons at P13-P15. 2. CP101,606 (10 microM) significantly decreased the amplitude of evoked N-EPSCs (eN-EPSCs) in visual cortical slices from rats at P3-P5, a developmental stage at which mRNA studies have indicated the virtual absence of NR2A mRNA. CP101,606 failed to significantly change evoked AMPA-mediated EPSCs at P5 and eN-EPSCs at P7-P8 and P13-P15. 3. NMDA receptor-mediated currents were also studied in somatic outside-out patches at P13-P15 with fast application of L-glutamate (1 mM). Haloperidol (50 microM) and CP101,606 (10 muM) blocked these currents in all patches tested. The effect of CP101,606 was concentration dependent. 4. We suggest that rather early in development synaptic receptors comprising NR1/NR2B subunits could be associated with other subunits so that blockade by haloperidol and CP101,606 is prevented. Moreover, the consistent blockade seen in outside out patches might be ascribed to the confinement of NR1/NR2B receptors to an extrasynaptic population.

UI	MeSH Term	Description	Entries
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010880	Piperidines	A family of hexahydropyridines.
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D004553	Electric Conductivity	The ability of a substrate to allow the passage of ELECTRONS.	Electrical Conductivity,Conductivity, Electric,Conductivity, Electrical
D006220	Haloperidol	A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)	Haldol
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000831	Animals, Newborn	Refers to animals in the period of time just after birth.	Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
D013569	Synapses	Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.	Synapse
D016194	Receptors, N-Methyl-D-Aspartate	A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.	N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D016202	N-Methylaspartate	An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).	N-Methyl-D-aspartate,NMDA,N-Methyl-D-aspartic Acid,Acid, N-Methyl-D-aspartic,N Methyl D aspartate,N Methyl D aspartic Acid,N Methylaspartate