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Science 27 November 1992:
Vol. 258. no. 5087, pp. 1498 - 1501
DOI: 10.1126/science.1359647
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Articles

Science, Vol 258, Issue 5087, 1498-1501
Copyright © 1992 by American Association for the Advancement of Science

articles

The time course of glutamate in the synaptic cleft

JD Clements, RA Lester, G Tong, CE Jahr, and GL Westbrook

Vollum Institute, Oregon Health Sciences University, Portland 97201.

The peak concentration and rate of clearance of neurotransmitter from the synaptic cleft are important determinants of synaptic function, yet the neurotransmitter concentration time course is unknown at synapses in the brain. The time course of free glutamate in the cleft was estimated by kinetic analysis of the displacement of a rapidly dissociating competitive antagonist from N-methyl-D-aspartate (NMDA) receptors during synaptic transmission. Glutamate peaked at 1.1 millimolar and decayed with a time constant of 1.2 milliseconds at cultured hippocampal synapses. This time course implies that transmitter saturates postsynaptic NMDA receptors. However, glutamate dissociates much more rapidly from alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Thus, the time course of free glutamate predicts that dissociation contributes to the decay of the AMPA receptor-mediated postsynaptic current.


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