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PMID:12890763
| Citation |
Tao, YX, Rumbaugh, G, Wang, GD, Petralia, RS, Zhao, C, Kauer, FW, Tao, F, Zhuo, M, Wenthold, RJ, Raja, SN, Huganir, RL, Bredt, DS and Johns, RA (2003) Impaired NMDA receptor-mediated postsynaptic function and blunted NMDA receptor-dependent persistent pain in mice lacking postsynaptic density-93 protein. J. Neurosci. 23:6703-12 |
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| Abstract |
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. |
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| Keywords |
Animals; Behavior, Animal; Cells, Cultured; Excitatory Postsynaptic Potentials/physiology; Female; Freund's Adjuvant; Guanylate Kinase; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Mice; Mice, Knockout; Nerve Tissue Proteins/biosynthesis; Nerve Tissue Proteins/deficiency; Nerve Tissue Proteins/genetics; Pain/chemically induced; Pain/genetics; Pain/physiopathology; Pain Measurement; Patch-Clamp Techniques; Posterior Horn Cells/cytology; Posterior Horn Cells/metabolism; Prosencephalon/metabolism; Receptors, N-Methyl-D-Aspartate/metabolism; Synaptic Transmission/genetics; Synaptic Transmission/physiology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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