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Integrins regulate NMDA receptor-mediated synaptic currents.

Bin Lin1, Amy C Arai, Gary Lynch

  • 1Department of Psychiatry and Human Behavior, University of California, Irvine 92612-1695, USA. blin@uci.edu

Journal of Neurophysiology
|May 13, 2003
PubMed
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Integrins, cell adhesion receptors, enhance N-methyl-d-aspartate (NMDA) receptor activity in synapses. This modulation occurs via the Src kinase pathway, impacting synaptic plasticity and long-term potentiation.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Synapses possess high concentrations of integrins, crucial adhesion receptors.
  • Integrins are implicated in long-term potentiation consolidation, suggesting a role in modulating synaptic glutamate receptors.

Purpose of the Study:

  • To investigate whether integrins modulate synaptic N-methyl-d-aspartate (NMDA)-type glutamate receptor activity.
  • To elucidate the mechanism by which integrins influence NMDA receptor function.

Main Methods:

  • Whole-cell clamp recordings of excitatory postsynaptic currents (EPSCs) in hippocampal slices.
  • Pharmacological blockade of AMPA-type and GABA(A) receptors.
  • Application of integrin ligand gly-arg-gly-asp-ser-pro (GRGDSP) and Src kinase inhibitors (PP2).

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Main Results:

  • Microperfusion of GRGDSP significantly increased NMDA receptor-gated synaptic current amplitude and duration.
  • GRGDSP did not alter paired-pulse facilitation, indicating no change in neurotransmitter release probability.
  • The Src kinase antagonist PP2, but not a control drug, abolished the GRGDSP-induced enhancement.

Conclusions:

  • Integrins exert potent modulatory effects on NMDA receptor operation.
  • Integrins likely act by regulating Src kinases, which are known to phosphorylate NMDA receptors.
  • This integrin-Src kinase-NMDA receptor pathway is critical for synaptic function and plasticity.