QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 30, 2003, 23(17):6703-6712

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (35) Citing Articles via Google Scholar Google Scholar Articles by Tao, Y.-X. Articles by Johns, R. A. Search for Related Content PubMed PubMed Citation Articles by Tao, Y.-X. Articles by Johns, R. A.

 Previous Article  |  Next Article 

Impaired NMDA Receptor-Mediated Postsynaptic Function and Blunted NMDA Receptor-Dependent Persistent Pain in Mice Lacking Postsynaptic Density-93 Protein

Yuan-Xiang Tao,^1 * Gavin Rumbaugh,^2 * Guo-Du Wang,^3 * Ronald S. Petralia,⁴ Chengshui Zhao,¹ Frederick W. Kauer,⁵ Feng Tao,¹ Min Zhuo,³ Robert J. Wenthold,⁴ Srinivasa N. Raja,¹ Richard L. Huganir,² David S. Bredt,⁵ and Roger A. Johns¹

¹Department of Anesthesiology and Critical Care Medicine and ²Howard Hughes Medical Institute, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, ³Washington University Pain Center, Departments of Anesthesiology, Anatomy and Neurobiology, and Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, ⁴Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, and ⁵Department of Physiology, University of California San Francisco, San Francisco, California 94143-0444

Modification of synaptic NMDA receptor (NMDAR) expression influences NMDAR-mediated synaptic function and associated persistent pain. NMDARs directly bind to a family of membrane-associated guanylate kinases (MAGUKs) that regulate surface and synaptic NMDAR trafficking in the CNS. We report here that postsynaptic density-93 protein (PSD-93), a postsynaptic neuronal MAGUK, is expressed abundantly in spinal dorsal horn and forebrain, where it colocalizes and interacts with NMDAR subunits NR2A and NR2B. Targeted disruption of the PSD-93 gene reduces not only surface NR2A and NR2B expression but also NMDAR-mediated excitatory postsynaptic currents and potentials, without affecting surface AMPA receptor expression or its synaptic function, in the regions mentioned above. Furthermore, mice lacking PSD-93 exhibit blunted NMDAR-dependent persistent pain induced by peripheral nerve injury or injection of Complete Freund's Adjuvant, although they display intact nociceptive responsiveness to acute pain. PSD-93 appears to be important for NMDAR synaptic targeting and function and to be a potential biochemical target for the treatment of persistent pain.

Key words: PSD-93; NMDA receptors; surface expression; persistent pain; spinal cord, forebrain

---

Received Mar. 4, 2003; revised Jun. 4, 2003; accepted Jun. 10, 2003.

This article has been cited by other articles:

				J.-S. Park, N. Voitenko, R. S. Petralia, X. Guan, J.-T. Xu, J. P. Steinberg, K. Takamiya, A. Sotnik, O. Kopach, R. L. Huganir, et al. Persistent Inflammation Induces GluR2 Internalization via NMDA Receptor-Triggered PKC Activation in Dorsal Horn Neurons J. Neurosci., March 11, 2009; 29(10): 3206 - 3219. [Abstract] [Full Text] [PDF]

				M. Conway, N. White, C. St. Jean, W. T. Zempsky, and K. Steven Use of Continuous Intravenous Ketamine for End-Stage Cancer Pain in Children Journal of Pediatric Oncology Nursing, March 1, 2009; 26(2): 100 - 106. [Abstract] [PDF]

				C. M. McDermott, M. N. Hardy, N. G. Bazan, and J. C. Magee Sleep deprivation-induced alterations in excitatory synaptic transmission in the CA1 region of the rat hippocampus J. Physiol., February 1, 2006; 570(3): 553 - 565. [Abstract] [Full Text] [PDF]

				T. Ravasi, H. Suzuki, K. C. Pang, S. Katayama, M. Furuno, R. Okunishi, S. Fukuda, K. Ru, M. C. Frith, M. M. Gongora, et al. Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome Genome Res., January 1, 2006; 16(1): 11 - 19. [Abstract] [Full Text] [PDF]

				L.-J. Wu, H. Toyoda, M.-G. Zhao, Y.-S. Lee, J. Tang, S. W. Ko, Y. H. Jia, F. W. F. Shum, C. V. Zerbinatti, G. Bu, et al. Upregulation of Forebrain NMDA NR2B Receptors Contributes to Behavioral Sensitization after Inflammation J. Neurosci., November 30, 2005; 25(48): 11107 - 11116. [Abstract] [Full Text] [PDF]

				C. I. Nam and L. Chen Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter PNAS, April 26, 2005; 102(17): 6137 - 6142. [Abstract] [Full Text] [PDF]

				Y. Lin, V. A. Skeberdis, A. Francesconi, M. V. L. Bennett, and R. S. Zukin Postsynaptic Density Protein-95 Regulates NMDA Channel Gating and Surface Expression J. Neurosci., November 10, 2004; 24(45): 10138 - 10148. [Abstract] [Full Text] [PDF]

				H. J. Chung, Y. H. Huang, L.-F. Lau, and R. L. Huganir Regulation of the NMDA Receptor Complex and Trafficking by Activity-Dependent Phosphorylation of the NR2B Subunit PDZ Ligand J. Neurosci., November 10, 2004; 24(45): 10248 - 10259. [Abstract] [Full Text] [PDF]

				M. L. Leyland and C. Dart An Alternatively Spliced Isoform of PSD-93/Chapsyn 110 Binds to the Inwardly Rectifying Potassium Channel, Kir2.1 J. Biol. Chem., October 15, 2004; 279(42): 43427 - 43436. [Abstract] [Full Text] [PDF]

				R.-R. Ji and G. Strichartz Cell Signaling and the Genesis of Neuropathic Pain Sci. Signal., September 28, 2004; 2004(252): re14 - re14. [Abstract] [Full Text] [PDF]

				Y.-X. Tao and R. A. Johns NEURONAL PDZ DOMAINS: A Promising New Molecular Target for Inhaled Anesthetics? Mol. Interv., August 1, 2004; 4(4): 215 - 221. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help