![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
J Zhong, SL Russell, DB Pritchett, PB Molinoff and K Williams
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104-6084.
The expression of mRNAs encoding subunits of the N-methyl-D-aspartate (NMDA) receptor was examined in cortical neurons maintained in primary culture. Cultures were prepared from embryonic day 17 rat neocortex. At this developmental age, levels of NR1, NR2A, NR2B, and NR2C mRNA were low or undetectable. Expression of NR1 mRNA increased progressively between days 1 and 21 in vitro. The amount of NR2A mRNA did not change between days 1 and 7 but increased between days 7 and 21. In contrast, levels of NR2B mRNA increased between days 1 and 7, with little further change after day 7. The level of NR2B mRNA was approximately 4-fold higher than that of NR2A mRNA in 21-day cultures. Using ligand binding assays, the proportion of NMDA receptors having a low affinity for ifenprodil was also found to increase over time in culture. The increase in the expression of receptors having a low affinity for ifenprodil and the increase in NR1 and NR2A mRNAs were reduced or prevented by maintaining cells in medium with a low concentration of serum. The results are consistent with the hypothesis that inclusion of the NR2A subunit in native NMDA receptors is responsible for their low affinity for ifenprodil. Splice variants of NR1 lacking the 5' (amino- terminal) insert were found to be the predominant forms of NR1 in cultured neurons. Variants containing the 5' insert represented only a small (< or = 5%) fraction of total NR1 mRNA, and their proportion was not altered as a function of time in culture. Time-dependent changes in the properties of NMDA receptors and in the expression of subunit mRNA occurring in cultured neurons are similar to changes observed in developing rat brain. Thus, the developmental sequence of NMDA receptor expression that occurs in vivo is partially retained in neurons maintained in vitro.
This article has been cited by other articles:
|
|
 |
|
  A. Qian and J. W. Johnson Permeant Ion Effects on External Mg2+ Block of NR1/2D NMDA Receptors. J. Neurosci., October 18, 2006; 26(42): 10899 - 10910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Alex, A. J. Baucum, and K. S. Wilcox Effect of Conantokin G on NMDA Receptor-Mediated Spontaneous EPSCs in Cultured Cortical Neurons J Neurophysiol, September 1, 2006; 96(3): 1084 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Thomas, A. J. Miller, and G. L. Westbrook Synaptic and Extrasynaptic NMDA Receptor NR2 Subunits in Cultured Hippocampal Neurons J Neurophysiol, March 1, 2006; 95(3): 1727 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Kinney, C. N. Davis, I. Tabarean, B. Conti, T. Bartfai, and M. M. Behrens A Specific Role for NR2A-Containing NMDA Receptors in the Maintenance of Parvalbumin and GAD67 Immunoreactivity in Cultured Interneurons J. Neurosci., February 1, 2006; 26(5): 1604 - 1615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Blanpied, R. J. Clarke, and J. W. Johnson Amantadine Inhibits NMDA Receptors by Accelerating Channel Closure during Channel Block J. Neurosci., March 30, 2005; 25(13): 3312 - 3322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Qian, A. L. Buller, and J. W. Johnson NR2 subunit-dependence of NMDA receptor channel block by external Mg2+ J. Physiol., January 15, 2005; 562(2): 319 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Li, Y. Otsu, T. H. Murphy, and L. A. Raymond Developmental Decrease in NMDA Receptor Desensitization Associated with Shift to Synapse and Interaction with Postsynaptic Density-95 J. Neurosci., December 3, 2003; 23(35): 11244 - 11254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Desai, D. Turetsky, K. Vasudevan, and A. Buonanno Analysis of Transcriptional Regulatory Sequences of the N-Methyl-D-aspartate Receptor 2A Subunit Gene in Cultured Cortical Neurons and Transgenic Mice J. Biol. Chem., November 22, 2002; 277(48): 46374 - 46384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Heidinger, P. Manzerra, X. Q. Wang, U. Strasser, S.-P. Yu, D. W. Choi, and M. M. Behrens Metabotropic Glutamate Receptor 1-Induced Upregulation of NMDA Receptor Current: Mediation through the Pyk2/Src-Family Kinase Pathway in Cortical Neurons J. Neurosci., July 1, 2002; 22(13): 5452 - 5461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Umemiya, N. Chen, L. A. Raymond, and T. H. Murphy A Calcium-Dependent Feedback Mechanism Participates in Shaping Single NMDA Miniature EPSCs J. Neurosci., January 1, 2001; 21(1): 1 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Sinor, S. Du, S. Venneti, R. C. Blitzblau, D. N. Leszkiewicz, P. A. Rosenberg, and E. Aizenman NMDA and Glutamate Evoke Excitotoxicity at Distinct Cellular Locations in Rat Cortical Neurons In Vitro J. Neurosci., December 1, 2000; 20(23): 8831 - 8837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Aizenman, J. D. Sinor, J. C. Brimecombe, and G. A. Herin Alterations of N-Methyl-D-aspartate Receptor Properties after Chemical Ischemia J. Pharmacol. Exp. Ther., November 1, 2000; 295(2): 572 - 577. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Li-Smerin, E. Aizenman, and J. W. Johnson Inhibition by Intracellular Mg2+ of Recombinant N-Methyl-D-aspartate Receptors Expressed in Chinese Hamster Ovary Cells J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 1104 - 1110. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. M. Antonov and J. W. Johnson Permeant ion regulation of N-methyl-D-aspartate receptor channel block by Mg2+ PNAS, December 7, 1999; 96(25): 14571 - 14576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Boxer, H. Moreno, B. Rudy, and E. B. Ziff FGF-2 Potentiates Ca2+-Dependent Inactivation of NMDA Receptor Currents in Hippocampal Neurons J Neurophysiol, December 1, 1999; 82(6): 3367 - 3377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Tovar and G. L. Westbrook The Incorporation of NMDA Receptors with a Distinct Subunit Composition at Nascent Hippocampal Synapses In Vitro J. Neurosci., May 15, 1999; 19(10): 4180 - 4188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Danysz and C. G. Parsons Glycine and N-Methyl-D-Aspartate Receptors: Physiological Significance and Possible Therapeutic Applications Pharmacol. Rev., December 1, 1998; 50(4): 597 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Arden, J. D. Sinor, W. K. Potthoff, and E. Aizenman Subunit-specific Interactions of Cyanide with the N-Methyl-D-aspartate Receptor J. Biol. Chem., August 21, 1998; 273(34): 21505 - 21511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Brimecombe, M. J. Gallagher, D. R. Lynch, and E. Aizenman An NR2B Point Mutation Affecting Haloperidol and CP101,606 Sensitivity of Single Recombinant N-Methyl-D-Aspartate Receptors J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 627 - 634. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. J. Maxwell, R. G. Goldie, and P. J. Henry Altered ETB- but not ETA-receptor density and function in sheep airway smooth muscle cells in culture Am J Physiol Lung Cell Mol Physiol, June 1, 1998; 274(6): L951 - L957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Fischer, V. Mutel, G. Trube, P. Malherbe, J. N. C. Kew, E. Mohacsi, M. P. Heitz, and J. A. Kemp Ro 25-6981, a Highly Potent and Selective Blocker of N-Methyl-D-aspartate Receptors Containing the NR2B Subunit. Characterization in Vitro J. Pharmacol. Exp. Ther., December 1, 1997; 283(3): 1285 - 1292. [Abstract] [Full Text]
|
|
|
|
|
|
M. J. Gallagher, H. Huang, E. R. Grant, and D. R. Lynch The NR2B-specific Interactions of Polyamines and Protons with the N-Methyl-D-aspartate Receptor J. Biol. Chem., October 3, 1997; 272(40): 24971 - 24979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Brimecombe, F. A. Boeckman, and E. Aizenman Functional consequences of NR2 subunit composition in single recombinant N-methyl-D-aspartate receptors PNAS, September 30, 1997; 94(20): 11019 - 11024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Whittemore, V. I. Ilyin, and R. M. Woodward Antagonism of N-Methyl-D-Aspartate Receptors by sigma Site Ligands: Potency, Subtype-Selectivity and Mechanisms of Inhibition J. Pharmacol. Exp. Ther., July 1, 1997; 282(1): 326 - 338. [Abstract] [Full Text]
|
|
|
|
|
|
A. C. Flint, U. S. Maisch, J. H. Weishaupt, A. R. Kriegstein, and H. Monyer NR2A Subunit Expression Shortens NMDA Receptor Synaptic Currents in Developing Neocortex J. Neurosci., April 1, 1997; 17(7): 2469 - 2476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Blanpied, F. A. Boeckman, E. Aizenman, and J. W. Johnson Trapping Channel Block of NMDA-Activated Responses By Amantadine and Memantine J Neurophysiol, January 1, 1997; 77(1): 309 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Follesa and M. K. Ticku Chronic Ethanol-mediated Up-regulation of the N-Methyl-D-aspartate Receptor Polypeptide Subunits in Mouse Cortical Neurons in Culture J. Biol. Chem., June 7, 1996; 271(23): 13297 - 13299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Wood, H. M. A. VanDongen, and A. M. J. VanDongen The 5`-Untranslated Region of the N-Methyl-D-aspartate Receptor NR2A Subunit Controls Efficiency of Translation J. Biol. Chem., April 5, 1996; 271(14): 8115 - 8120. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
