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 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.
Vollum Institute, Oregon Health Sciences University, Portland 97201.
J D
JD
Clements
R A
RA
Lester
G
G
Tong
C E
CE
Jahr
G L
GL
Westbrook
D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D005971:Glutamates; D018377:Neurotransmitter Agents; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D015074:2-Aminoadipic Acid; D018698:Glutamic Acid; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid