Increased Contribution of NR2A Subunit to Synaptic NMDA Receptors in Developing Rat Cortical Neurons

Overview

Journal J Physiol

Specialty Physiology

Date 1998 Apr 4

PMID 9490809

Citations 179

Authors

G Stocca

S Vicini

Affiliations

Soon will be listed here.

Abstract

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.

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References

Zukin R, Bennett M . Alternatively spliced isoforms of the NMDARI receptor subunit. Trends Neurosci. 1995; 18(7):306-13. DOI: 10.1016/0166-2236(95)93920-s. View

Chenard B, Bordner J, Butler T, Chambers L, Collins M, De Costa D . (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol: a potent new neuroprotectant which blocks N-methyl-D-aspartate responses. J Med Chem. 1995; 38(16):3138-45. DOI: 10.1021/jm00016a017. View

Priestley T, Laughton P, Myers J, Le BOURDELLES B, Kerby J, Whiting P . Pharmacological properties of recombinant human N-methyl-D-aspartate receptors comprising NR1a/NR2A and NR1a/NR2B subunit assemblies expressed in permanently transfected mouse fibroblast cells. Mol Pharmacol. 1995; 48(5):841-8. View

Behe P, Stern P, Wyllie D, Nassar M, Schoepfer R, Colquhoun D . Determination of NMDA NR1 subunit copy number in recombinant NMDA receptors. Proc Biol Sci. 1995; 262(1364):205-13. DOI: 10.1098/rspb.1995.0197. View

Mori H, Mishina M . Structure and function of the NMDA receptor channel. Neuropharmacology. 1995; 34(10):1219-37. DOI: 10.1016/0028-3908(95)00109-j. View

Takahashi T, Feldmeyer D, Suzuki N, Onodera K, Cull-Candy S, Sakimura K . Functional correlation of NMDA receptor epsilon subunits expression with the properties of single-channel and synaptic currents in the developing cerebellum. J Neurosci. 1996; 16(14):4376-82. PMC: 6578868. View

Boeckman F, Aizenman E . Pharmacological properties of acquired excitotoxicity in Chinese hamster ovary cells transfected with N-methyl-D-aspartate receptor subunits. J Pharmacol Exp Ther. 1996; 279(2):515-23. View

Kirson E, Yaari Y . Synaptic NMDA receptors in developing mouse hippocampal neurones: functional properties and sensitivity to ifenprodil. J Physiol. 1996; 497 ( Pt 2):437-55. PMC: 1160995. DOI: 10.1113/jphysiol.1996.sp021779. View

Ilyin V, Whittemore E, Guastella J, Weber E, Woodward R . Subtype-selective inhibition of N-methyl-D-aspartate receptors by haloperidol. Mol Pharmacol. 1996; 50(6):1541-50. View

10.

Clark B, Farrant M, Cull-Candy S . A direct comparison of the single-channel properties of synaptic and extrasynaptic NMDA receptors. J Neurosci. 1997; 17(1):107-16. PMC: 6793703. View

11.

Gotz T, Kraushaar U, Geiger J, Lubke J, Berger T, Jonas P . Functional properties of AMPA and NMDA receptors expressed in identified types of basal ganglia neurons. J Neurosci. 1997; 17(1):204-15. PMC: 6793708. View

12.

Yu X, Askalan R, Keil 2nd G, Salter M . NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science. 1997; 275(5300):674-8. DOI: 10.1126/science.275.5300.674. View

13.

Luo J, Wang Y, Yasuda R, Dunah A, Wolfe B . The majority of N-methyl-D-aspartate receptor complexes in adult rat cerebral cortex contain at least three different subunits (NR1/NR2A/NR2B). Mol Pharmacol. 1997; 51(1):79-86. DOI: 10.1124/mol.51.1.79. View

14.

Plant T, Schirra C, Garaschuk O, Rossier J, Konnerth A . Molecular determinants of NMDA receptor function in GABAergic neurones of rat forebrain. J Physiol. 1997; 499 ( Pt 1):47-63. PMC: 1159336. DOI: 10.1113/jphysiol.1997.sp021910. View

15.

Flint A, Maisch U, Weishaupt J, Kriegstein A, Monyer H . NR2A subunit expression shortens NMDA receptor synaptic currents in developing neocortex. J Neurosci. 1997; 17(7):2469-76. PMC: 6573498. View

16.

Hamill O, Marty A, Neher E, Sakmann B, Sigworth F . Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981; 391(2):85-100. DOI: 10.1007/BF00656997. View

17.

Lester R, Jahr C . NMDA channel behavior depends on agonist affinity. J Neurosci. 1992; 12(2):635-43. PMC: 6575615. View

18.

HESTRIN S . Developmental regulation of NMDA receptor-mediated synaptic currents at a central synapse. Nature. 1992; 357(6380):686-9. DOI: 10.1038/357686a0. View

19.

Carmignoto G, Vicini S . Activity-dependent decrease in NMDA receptor responses during development of the visual cortex. Science. 1992; 258(5084):1007-11. DOI: 10.1126/science.1279803. View

20.

Colquhoun D, Jonas P, Sakmann B . Action of brief pulses of glutamate on AMPA/kainate receptors in patches from different neurones of rat hippocampal slices. J Physiol. 1992; 458:261-87. PMC: 1175155. DOI: 10.1113/jphysiol.1992.sp019417. View