 |
 Previous Article | Next Article 
Volume 17, Number 12,
Issue of June 15, 1997
pp. 4672-4687
Copyright ©1997 Society for Neuroscience
Transporters Buffer Synaptically Released Glutamate on a
Submillisecond Time Scale
Received Feb. 4, 1997; revised April 7, 1997; accepted April 8, 1997.
Jeffrey S. Diamond and
Craig E. Jahr
The Vollum Institute, Oregon Health Sciences University,
Portland, Oregon 97201
The role of transporters in clearing free glutamate from the
synaptic cleft was studied in rat CA1 hippocampal neurons cultured on
glial microislands. The time course of free glutamate in the cleft
during a synaptic event was estimated by measuring the extent to which
the rapidly dissociating AMPA receptor antagonist kynurenate (KYN) was
replaced by glutamate during a synaptic response. Dose inhibition of
the AMPA receptor EPSC by KYN was less than predicted by the
equilibrium affinity of the antagonist, and the rise time of AMPA
receptor miniature EPSCs (mEPSCs) was slowed by KYN. Both results
indicated that KYN dissociated from AMPA receptors and was replaced by
synaptically released transmitter. When transporters were blocked by
D,L-threo- -hydroxyaspartic acid
(THA) or Li+, the mEPSC rise time in the presence of
KYN was slowed further, indicating that transporters affect the
glutamate concentration in the first few hundred microseconds of the
synaptic response.
The glutamate transient necessary to cause these effects was determined
by developing a detailed kinetic model of the AMPA receptor. The model
replicated the effects of KYN on the amplitude and rise time of the
synaptic responses when driven by glutamate transients that were
similar to previous estimates (; ).
The effects of THA were replicated by slowing and enlarging the slower
phase of the dual component transient by about 20% or by prolonging
the single component by almost 40%. Because transport is too slow to
account for these effects, it is concluded that transporters buffer
glutamate in the synaptic cleft.
Key words:
glutamate transporters;
AMPA receptor;
kinetic
model;
cultured hippocampal neurons;
buffered diffusion;
miniature
EPSC;
kynurenate;
D,L-threo--hydroxyaspartic acid
(THA)
This article has been cited by other articles:
|
|
|
|
 
E. Garcia-Perez, D. C. Lo, and J. F. Wesseling
Kinetic Isolation of a Slowly Recovering Component of Short-Term Depression During Exhaustive Use at Excitatory Hippocampal Synapses
J Neurophysiol,
August 1, 2008;
100(2):
781 - 795.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Beato
The Time Course of Transmitter at Glycinergic Synapses onto Motoneurons
J. Neurosci.,
July 16, 2008;
28(29):
7412 - 7425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Balland, P. Lachamp, J.-P. Kessler, and F. Tell
Silent Synapses in Developing Rat Nucleus Tractus Solitarii Have AMPA Receptors
J. Neurosci.,
April 30, 2008;
28(18):
4624 - 4634.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Heine, L. Groc, R. Frischknecht, J.-C. Beique, B. Lounis, G. Rumbaugh, R. L. Huganir, L. Cognet, and D. Choquet
Surface Mobility of Postsynaptic AMPARs Tunes Synaptic Transmission
Science,
April 11, 2008;
320(5873):
201 - 205.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Liu and C. Chen
Different Roles for AMPA and NMDA Receptors in Transmission at the Immature Retinogeniculate Synapse
J Neurophysiol,
February 1, 2008;
99(2):
629 - 643.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Herman and C. E. Jahr
Extracellular Glutamate Concentration in Hippocampal Slice
J. Neurosci.,
September 5, 2007;
27(36):
9736 - 9741.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Xu, H. Peng, N. Kang, Z. Zhao, J. H-C. Lin, P. K. Stanton, and J. Kang
Glutamate-induced Exocytosis of Glutamate from Astrocytes
J. Biol. Chem.,
August 17, 2007;
282(33):
24185 - 24197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Pei, M. Ritz, M. McCarthy, Z. Huang, and L. Niu
Receptor Occupancy and Channel-opening Kinetics: A STUDY OF GLUR1 L497Y AMPA RECEPTOR
J. Biol. Chem.,
August 3, 2007;
282(31):
22731 - 22736.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Pinheiro, D. Perrais, F. Coussen, J. Barhanin, B. Bettler, J. R. Mann, J. O. Malva, S. F. Heinemann, and C. Mulle
GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses
PNAS,
July 17, 2007;
104(29):
12181 - 12186.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Patten and D. W. Ali
AMPA receptors associated with zebrafish Mauthner cells switch subunits during development
J. Physiol.,
June 15, 2007;
581(3):
1043 - 1056.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. P. Habets and J. G. G. Borst
Dynamics of the readily releasable pool during post-tetanic potentiation in the rat calyx of Held synapse
J. Physiol.,
June 1, 2007;
581(2):
467 - 478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Schwartz, T. Blackmer, T. Gerachshenko, and S. Alford
Presynaptic G-Protein-Coupled Receptors Regulate Synaptic Cleft Glutamate via Transient Vesicle Fusion
J. Neurosci.,
May 30, 2007;
27(22):
5857 - 5868.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Crowley, A. G. Carter, and W. G. Regehr
Fast Vesicle Replenishment and Rapid Recovery from Desensitization at a Single Synaptic Release Site
J. Neurosci.,
May 16, 2007;
27(20):
5448 - 5460.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ertunc, Y. Sara, C. Chung, D. Atasoy, T. Virmani, and E. T. Kavalali
Fast Synaptic Vesicle Reuse Slows the Rate of Synaptic Depression in the CA1 Region of Hippocampus
J. Neurosci.,
January 10, 2007;
27(2):
341 - 354.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Lang, C. Bohmer, M. Palmada, G. Seebohm, N. Strutz-Seebohm, and V. Vallon
(Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms.
Physiol Rev,
October 1, 2006;
86(4):
1151 - 1178.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Cechova and Z. Zuo
Inhibition of glutamate transporters increases the minimum alveolar concentration for isoflurane in rats
Br. J. Anaesth.,
August 1, 2006;
97(2):
192 - 195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ma, S. Zheng, and Z. Zuo
The Transcription Factor Regulatory Factor X1 Increases the Expression of Neuronal Glutamate Transporter Type 3
J. Biol. Chem.,
July 28, 2006;
281(30):
21250 - 21255.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Jungling, V. Eulenburg, R. Moore, R. Kemler, V. Lessmann, and K. Gottmann
N-cadherin transsynaptically regulates short-term plasticity at glutamatergic synapses in embryonic stem cell-derived neurons.
J. Neurosci.,
June 28, 2006;
26(26):
6968 - 6978.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gebhardt and S. G. Cull-Candy
Influence of agonist concentration on AMPA and kainate channels in CA1 pyramidal cells in rat hippocampal slices
J. Physiol.,
June 1, 2006;
573(2):
371 - 394.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Nieus, E. Sola, J. Mapelli, E. Saftenku, P. Rossi, and E. D'Angelo
LTP Regulates Burst Initiation and Frequency at Mossy Fiber-Granule Cell Synapses of Rat Cerebellum: Experimental Observations and Theoretical Predictions
J Neurophysiol,
February 1, 2006;
95(2):
686 - 699.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. I. Wadiche, A. V. Tzingounis, and C. E. Jahr
Intrinsic kinetics determine the time course of neuronal synaptic transporter currents
PNAS,
January 24, 2006;
103(4):
1083 - 1087.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Matsui, C. E. Jahr, and M. E. Rubio
High-Concentration Rapid Transients of Glutamate Mediate Neural-Glial Communication via Ectopic Release
J. Neurosci.,
August 17, 2005;
25(33):
7538 - 7547.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bicho and C. Grewer
Rapid Substrate-Induced Charge Movements of the GABA Transporter GAT1
Biophys. J.,
July 1, 2005;
89(1):
211 - 231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Zuo and H. Fang
Glutamate transporter type 3 attenuates the activation of N-methy-D-aspartate receptors co-expressed in Xenopus oocytes
J. Exp. Biol.,
June 1, 2005;
208(11):
2063 - 2070.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. J. Bannister, T. A. Benke, J. Mellor, H. Scott, E. Gurdal, J. W. Crabtree, and J. T. R. Isaac
Developmental Changes in AMPA and Kainate Receptor-Mediated Quantal Transmission at Thalamocortical Synapses in the Barrel Cortex
J. Neurosci.,
May 25, 2005;
25(21):
5259 - 5271.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Huang and Z. Zuo
Isoflurane Induces a Protein Kinase C {alpha}-Dependent Increase in Cell-Surface Protein Level and Activity of Glutamate Transporter Type 3
Mol. Pharmacol.,
May 1, 2005;
67(5):
1522 - 1533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L. Moulder and S. Mennerick
Reluctant Vesicles Contribute to the Total Readily Releasable Pool in Glutamatergic Hippocampal Neurons
J. Neurosci.,
April 13, 2005;
25(15):
3842 - 3850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Diamond
Deriving the Glutamate Clearance Time Course from Transporter Currents in CA1 Hippocampal Astrocytes: Transmitter Uptake Gets Faster during Development
J. Neurosci.,
March 16, 2005;
25(11):
2906 - 2916.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Schenk, E. Menna, T. Kim, M. Passafaro, S. Chang, P. De Camilli, and M. Matteoli
A Novel Pathway for Presynaptic Mitogen-Activated Kinase Activation via AMPA Receptors
J. Neurosci.,
February 16, 2005;
25(7):
1654 - 1663.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Matsui and C. E. Jahr
Differential Control of Synaptic and Ectopic Vesicular Release of Glutamate
J. Neurosci.,
October 13, 2004;
24(41):
8932 - 8939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Raghavachari and J. E. Lisman
Properties of Quantal Transmission at CA1 Synapses
J Neurophysiol,
October 1, 2004;
92(4):
2456 - 2467.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. H. Huang, S. R. Sinha, K. Tanaka, J. D. Rothstein, and D. E. Bergles
Astrocyte Glutamate Transporters Regulate Metabotropic Glutamate Receptor-Mediated Excitation of Hippocampal Interneurons
J. Neurosci.,
May 12, 2004;
24(19):
4551 - 4559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Brasnjo and T. S. Otis
Isolation of glutamate transport-coupled charge flux and estimation of glutamate uptake at the climbing fiber-Purkinje cell synapse
PNAS,
April 20, 2004;
101(16):
6273 - 6278.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. A. Rameau, L.-Y. Chiu, and E. B. Ziff
Bidirectional Regulation of Neuronal Nitric-oxide Synthase Phosphorylation at Serine 847 by the N-Methyl-D-aspartate Receptor
J. Biol. Chem.,
April 2, 2004;
279(14):
14307 - 14314.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. P. Larsson, A. V. Tzingounis, H. P. Koch, and M. P. Kavanaugh
Fluorometric measurements of conformational changes in glutamate transporters
PNAS,
March 16, 2004;
101(11):
3951 - 3956.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. H. Huang, M. Dykes-Hoberg, K. Tanaka, J. D. Rothstein, and D. E. Bergles
Climbing Fiber Activation of EAAT4 Transporters and Kainate Receptors in Cerebellar Purkinje Cells
J. Neurosci.,
January 7, 2004;
24(1):
103 - 111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. XU-FRIEDMAN and W. G. REGEHR
Structural Contributions to Short-Term Synaptic Plasticity
Physiol Rev,
January 1, 2004;
84(1):
69 - 85.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Silver, J. Lubke, B. Sakmann, and D. Feldmeyer
High-Probability Uniquantal Transmission at Excitatory Synapses in Barrel Cortex
Science,
December 12, 2003;
302(5652):
1981 - 1984.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. Singer and J. S. Diamond
Sustained Ca2+ Entry Elicits Transient Postsynaptic Currents at a Retinal Ribbon Synapse
J. Neurosci.,
November 26, 2003;
23(34):
10923 - 10933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zhang and D. Sulzer
Glutamate Spillover in the Striatum Depresses Dopaminergic Transmission by Activating Group I Metabotropic Glutamate Receptors
J. Neurosci.,
November 19, 2003;
23(33):
10585 - 10592.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Voutsinos-Porche, G. Knott, K. Tanaka, C. Quairiaux, E. Welker, and G. Bonvento
Glial Glutamate Transporters and Maturation of the Mouse Somatosensory Cortex
Cereb Cortex,
October 1, 2003;
13(10):
1110 - 1121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Lowe
Flash Photolysis Reveals a Diversity of Ionotropic Glutamate Receptors on the Mitral Cell Somatodendritic Membrane
J Neurophysiol,
September 1, 2003;
90(3):
1737 - 1746.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Y. C. Wong, B. P. Graham, B. Billups, and I. D. Forsythe
Distinguishing between Presynaptic and Postsynaptic Mechanisms of Short-Term Depression during Action Potential Trains
J. Neurosci.,
June 15, 2003;
23(12):
4868 - 4877.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yamashita, T. Ishikawa, and T. Takahashi
Developmental Increase in Vesicular Glutamate Content Does Not Cause Saturation of AMPA Receptors at the Calyx of Held Synapse
J. Neurosci.,
May 1, 2003;
23(9):
3633 - 3638.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Conti and J. Lisman
The high variance of AMPA receptor- and NMDA receptor-mediated responses at single hippocampal synapses: Evidence for multiquantal release
PNAS,
April 15, 2003;
100(8):
4885 - 4890.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Schwartz, R. D. Blakely, and L. J. DeFelice
Binding and Transport in Norepinephrine Transporters. REAL-TIME, SPATIALLY RESOLVED ANALYSIS IN SINGLE CELLS USING A FLUORESCENT SUBSTRATE
J. Biol. Chem.,
March 7, 2003;
278(11):
9768 - 9777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bordey and H. Sontheimer
Modulation of Glutamatergic Transmission by Bergmann Glial Cells in Rat Cerebellum In Situ
J Neurophysiol,
February 1, 2003;
89(2):
979 - 988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. A. Kinney and W. J. Spain
Synaptically Evoked GABA Transporter Currents in Neocortical Glia
J Neurophysiol,
December 1, 2002;
88(6):
2899 - 2908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. F. Wesseling and D. C. Lo
Limit on the Role of Activity in Controlling the Release-Ready Supply of Synaptic Vesicles
J. Neurosci.,
November 15, 2002;
22(22):
9708 - 9720.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Franks, T. M. Bartol Jr., and T. J. Sejnowski
A Monte Carlo Model Reveals Independent Signaling at Central Glutamatergic Synapses
Biophys. J.,
November 1, 2002;
83(5):
2333 - 2348.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ikegaya, S. Matsuura, S. Ueno, A. Baba, M. K. Yamada, N. Nishiyama, and N. Matsuki
beta -Amyloid Enhances Glial Glutamate Uptake Activity and Attenuates Synaptic Efficacy
J. Biol. Chem.,
August 23, 2002;
277(35):
32180 - 32186.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Grunewald, D. Menaker, and B. I. Kanner
Cysteine-scanning Mutagenesis Reveals a Conformationally Sensitive Reentrant Pore-Loop in the Glutamate Transporter GLT-1
J. Biol. Chem.,
July 12, 2002;
277(29):
26074 - 26080.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. P. Lehre and D. A. Rusakov
Asymmetry of Glia near Central Synapses Favors Presynaptically Directed Glutamate Escape
Biophys. J.,
July 1, 2002;
83(1):
125 - 134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Borre, M. P. Kavanaugh, and B. I. Kanner
Dynamic Equilibrium between Coupled and Uncoupled Modes of a Neuronal Glutamate Transporter
J. Biol. Chem.,
April 12, 2002;
277(16):
13501 - 13507.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Reichelt and T. Knopfel
Glutamate Uptake Controls Expression of a Slow Postsynaptic Current Mediated by mGluRs in Cerebellar Purkinje Cells
J Neurophysiol,
April 1, 2002;
87(4):
1974 - 1980.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Chen and J. S. Diamond
Synaptically Released Glutamate Activates Extrasynaptic NMDA Receptors on Cells in the Ganglion Cell Layer of Rat Retina
J. Neurosci.,
March 15, 2002;
22(6):
2165 - 2173.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Scheuss, R. Schneggenburger, and E. Neher
Separation of Presynaptic and Postsynaptic Contributions to Depression by Covariance Analysis of Successive EPSCs at the Calyx of Held Synapse
J. Neurosci.,
February 1, 2002;
22(3):
728 - 739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Brocke, A. Bendahan, M. Grunewald, and B. I. Kanner
Proximity of Two Oppositely Oriented Reentrant Loops in the Glutamate Transporter GLT-1 Identified by Paired Cysteine Mutagenesis
J. Biol. Chem.,
February 1, 2002;
277(6):
3985 - 3992.
[Abstract]
[Full Text]
[PDF]
| |
