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J Neurophysiol (May 1, 2003). 10.1152/jn.00783.2002
Submitted on Submitted 10 September 2002; accepted in final form 9 January 2003
REPORT
1Department of Psychiatry and Human Behavior, University of California, Irvine, California 92612-1695; 2Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield, Illinois 62702; and 3Department of Anatomy and Neurobiology, University of California, Irvine, California 92697-1275
Lin, Bin,
Amy C. Arai,
Gary Lynch, and
Christine M. Gall.
Integrins Regulate NMDA Receptor-Mediated Synaptic Currents. J. Neurophysiol. 89: 2874-2878, 2003. Synapses contain high concentrations of integrins, adhesion receptors
known to influence the operation of neighboring transmembrane proteins.
Evidence that integrins are important for consolidation of long-term
potentiation suggests that these adhesion proteins may modulate
activities of synaptic glutamate receptors. The present study provides
a first test of the possibility that integrins modulate synaptic
N-methyl-D-aspartate (NMDA)-type glutamate
receptor activities. Excitatory postsynaptic currents (EPSCs) were
recorded with whole cell clamp from hippocampal slices in which
AMPA-type glutamate receptors and GABAA receptors
were pharmacologically blocked. Microperfusion of the peptide integrin
ligand gly-arg-gly-asp-ser-pro (GRGDSP) caused an approximately twofold
increase in the amplitude and duration of NMDA receptor-gated synaptic
currents. Control peptides had no effect. Paired-pulse facilitation was
unchanged, indicating that the ligand did not modify neurotransmitter
release probabilities. Infusion of the Src kinase antagonist PP2 but
not the control drug 4-amino-7-phenylpyrazolo[3,4-d]pyrimidine
eliminated the enhancing effect of GRGDSP. Integrins regulate Src
kinases that are known to phosphorylate NMDA receptors. It is concluded that integrins act through this route to exert potent modulatory effects on the operation of NMDA receptors.
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