Tao, Yuan-Xiang;
Rumbaugh, Gavin;
Wang, Guo-Du;
Petralia, Ronald S.;
Zhao, Chengshui;
Kauer, Frederick W.;
Tao, Feng;
Zhuo, Min;
Wenthold, Robert J.;
Raja, Srinivasa N.;
Huganir, Richard L.;
Bredt, David S.;
Johns, Roger A.
Impaired NMDA Receptor-Mediated Postsynaptic Function and Blunted NMDA Receptor-Dependent Persistent Pain in Mice Lacking Postsynaptic Density-93 Protein
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Medientyp:
E-Artikel
Titel:
Impaired NMDA Receptor-Mediated Postsynaptic Function and Blunted NMDA Receptor-Dependent Persistent Pain in Mice Lacking Postsynaptic Density-93 Protein
Beteiligte:
Tao, Yuan-Xiang;
Rumbaugh, Gavin;
Wang, Guo-Du;
Petralia, Ronald S.;
Zhao, Chengshui;
Kauer, Frederick W.;
Tao, Feng;
Zhuo, Min;
Wenthold, Robert J.;
Raja, Srinivasa N.;
Huganir, Richard L.;
Bredt, David S.;
Johns, Roger A.
Beschreibung:
<jats:p>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.</jats:p>