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(NAS Colloquium) The Neurobiology of Pain (1999) / Chapter Skim
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Src, a Molecular Switch Governing Gain Control of Synaptic Transmission Mediated by N-methyl-D-aspartate Receptors
Pages 7697-7704

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From page 7697...
... receptor is a principal subtype of glutamate receptor mediating fast excitatory transmission at synapses in the dorsal horn of the spinal cord and other regions of the central nervous system. NMDA receptors are crucial for the lasting enhancement of synaptic transmission that occurs both physiologically and in pathological conditions such as chronic pain.
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From page 7698...
... Therefore, it appears that removal of Zn2+ inhibition is not the means by which the function of native NMDA receptors is up-regulated by tyrosine phosphorylation. Thus, for native NMDA channels, the question of whether phosphorylation at the sites implicated by mutagenesis is the means for up-regulating NMDA channel function remains open.
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From page 7699...
... Whether Src is physically associated with NMDA channels could not be determined from any of the previous experiments: membrane patches are large in comparison with the size of the proteins that comprise ion channels, and confocal microscopy does not have sufficient spatial resolution. While it was therefore possible that Src was separate from the NMDA receptor complex, we found that Src and NMDA receptor subunit proteins coprecipitate, demonstrating that Src is associated with the NMDA channel complex.
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From page 7700...
... Sci. USA 96 (1999J Because the role of Src in LTP induction appears to be to enhance NMDA receptor function, one potential mechanism is phosphorylation of one of the NMDA receptor subunit proteins, as discussed above.
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From page 7701...
... A1SO7 depolarizing the cells by bath-applying a high-K+ solution to mimic the depolarization caused by applying the agonists did not affect NMDA channel function. Thus, we concluded that NMDA receptor function may be up-regulated by Na+ influx through neighboring glutamate receptors.
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From page 7702...
... 5. For simplicity of presentation, we represent the entire complex of NMDA channel subunits and associated proteins together as one pair of ovals forming the ion channel.
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From page 7703...
... i may be important for boosting synaptic NMDA receptor function and initiating the intracellular signaling cascades that produce persistent alterations in synaptic function. Because NMDA receptors are implicated in a variety of pathophysiological conditions in the CNS, the regulation by Src and Na+ represent potential targets for developing new types of therapeutic intervention in a variety of CNS disorders.
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From page 7704...
... 7704 Colloquium Paper: Yu and Salter 52. Tong, G., Shepherd, D
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Key Terms

  • nmda receptor
  • nmda channel
  • receptor function
  • nmda channels
  • channel activity

  • dorsal horn
  • synaptic transmission
  • subunit proteins
  • native nmda
  • channel function

  • receptor subunit
  • tyrosine phosphorylation
  • protein tyrosine
  • spinal cord
  • tyrosine kinase

  • lasting enhancement
  • channel gating
  • ltp induction
  • regulating nmda
  • nmda currents

  • endogenous ptk
  • ampa responses
  • central nervous
  • horn neurons
  • synaptic responses

  • membrane patches
  • glutamate receptor
  • ptk regulating
  • excitatory transmission
  • ion channels


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