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Journal of Neuroscience, Vol 16, 1634-1644, Copyright © 1996 by Society for Neuroscience
Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites
TS Otis, YC Wu and LO Trussell
Department of Neurophysiology, University of Wisconsin School of Medicine, Madison 53706, USA.
The roles of glutamate diffusion, uptake, and channel kinetics in shaping
the AMPA receptor EPSC were examined at a calyceal synapse. The EPSC decay
was described by three exponential components: two matching desensitizing
channel kinetics, and a third component at least 10 times slower. The
slowest component had identical voltage dependence to the steady-state AMPA
current and was selectively increased and prolonged by blockade of
glutamate uptake, indicating that the slow EPSC represented rebinding of
glutamate at partially desensitized AMPA receptors. The data were in strong
agreement with the predictions of a model of transmitter diffusion from
multiple release sites into a large synaptic cleft. Within the first
millisecond after release, transmitter concentrations in the cleft fell
below millimolar levels, causing the fastest parts of the EPSC to be shaped
by channel kinetics. The slowest component was determined by the removal
over tens of milliseconds of the final 10-100 microM glutamate by diffusion
and uptake. The data and modeling indicate that transmitter uptake and
cooperation between release sites are significant determinants of a slow
"tail" of glutamate in the synaptic cleft. This slow clearance of glutamate
is likely to limit postsynaptic receptor availability through
desensitization.
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