The Time Course of Glutamate in the Synaptic Cleft

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 an...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1992-11, Vol.258 (5087), p.1498-1501
Main Authors: Clements, John D., Robin A. J. Lester, Tong, Gang, Jahr, Craig E., Westbrook, Gary L.
Format: Article
Language:English
Subjects:
2-Aminoadipic Acid - pharmacology
Action Potentials - physiology
Animals
Biological and medical sciences
Brain
Cell physiology
Cells, Cultured
Dose response relationship
Feedback (Response)
Fundamental and applied biological sciences. Psychology
Glutamate
Glutamates - metabolism
Glutamic Acid
Hippocampus - cytology
Hippocampus - physiology
Inhibition
Kinetics
Modeling
Models, Neurological
Molecular and cellular biology
N methyl D aspartate receptors
Neural transmission
Neurons
Neurons - physiology
Neurotransmission
Neurotransmitter Agents - metabolism
Physiological aspects
Piperazines - pharmacology
Radio transmitters
Rats
Receptors
Receptors, N-Methyl-D-Aspartate - drug effects
Receptors, N-Methyl-D-Aspartate - physiology
Synapses
Synapses - drug effects
Synapses - metabolism
Synaptic transmission
Time constants
Time Factors
Transmitters
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Summary: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 α-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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1359647