Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites

Thomas S. Otis, Yuh Cherng Wu, Laurence Trussell

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

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 μM 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.

Original languageEnglish (US)
Pages (from-to)1634-1644
Number of pages11
JournalJournal of Neuroscience
Volume16
Issue number5
StatePublished - Mar 1 1996
Externally publishedYes

Fingerprint

Amino Acid Transport System X-AG
Synapses
Glutamic Acid
AMPA Receptors
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Keywords

  • AMPA receptor
  • channel kinetics
  • cochlear nucleus
  • desensitization
  • diffusion
  • nucleus magnocellularis
  • transmitter uptake

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites. / Otis, Thomas S.; Wu, Yuh Cherng; Trussell, Laurence.

In: Journal of Neuroscience, Vol. 16, No. 5, 01.03.1996, p. 1634-1644.

Research output: Contribution to journalArticle

@article{dcaa59b700e4490cabd2dc730aa77e05,
title = "Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites",
abstract = "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 μM 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.",
keywords = "AMPA receptor, channel kinetics, cochlear nucleus, desensitization, diffusion, nucleus magnocellularis, transmitter uptake",
author = "Otis, {Thomas S.} and Wu, {Yuh Cherng} and Laurence Trussell",
year = "1996",
month = "3",
day = "1",
language = "English (US)",
volume = "16",
pages = "1634--1644",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "5",

}

TY - JOUR

T1 - Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites

AU - Otis, Thomas S.

AU - Wu, Yuh Cherng

AU - Trussell, Laurence

PY - 1996/3/1

Y1 - 1996/3/1

N2 - 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 μM 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.

AB - 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 μM 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.

KW - AMPA receptor

KW - channel kinetics

KW - cochlear nucleus

KW - desensitization

KW - diffusion

KW - nucleus magnocellularis

KW - transmitter uptake

UR - http://www.scopus.com/inward/record.url?scp=0029915273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029915273&partnerID=8YFLogxK

M3 - Article

VL - 16

SP - 1634

EP - 1644

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 5

ER -