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Volume 17, Number 1,
Issue of January 1, 1997
pp. 58-69
Copyright ©1997 Society for Neuroscience
Single-Channel Properties of Recombinant AMPA Receptors Depend on
RNA Editing, Splice Variation, and Subunit Composition
Received July 8, 1996; revised Oct. 4, 1996; accepted Oct. 8, 1996.
Geoffrey T. Swanson1, 2, ,
Sunjeev K. Kamboj1, , and
Stuart G. Cull-Candy1
1 Department of Pharmacology, University College
London, London WC1E 6BT, United Kingdom, and 2 Molecular
Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037
Non-NMDA glutamate receptor subunits of the AMPA-preferring
subfamily combine to form ion channels with heterogeneous functional properties. We have investigated the effects of RNA editing at the Q/R
site, splice variation of the "flip/flop" cassette, and multimeric
subunit assembly on the single-channel conductance and kinetic
properties of the recombinant AMPA receptors formed from GluR2 and
GluR4 expressed in HEK 293 cells. We found that AMPA receptor
single-channel conductance was dependent on the Q/R site editing state
of the subunits comprising the channel. Calcium-permeable (unedited)
channels had resolvable single-channel events with main conductance
states of 7-8 pS, whereas fully edited GluR2 channels had very low
conductances of ~300 fS (estimated from noise analysis).
Additionally, the flip splice variant of GluR4 conferred
agonist-dependent conductance properties reminiscent of those found for
a subset of AMPA receptors in cultured cerebellar granule cells. These
results provide a description of the single-channel properties of
certain recombinant AMPA receptors and suggest that the single-channel
conductance may be determined by the expression of edited GluR2
subunits in neurons.
Key words:
glutamate receptor;
AMPA receptor;
single-channel
conductance;
RNA editing;
alternative splicing;
patch-clamp
electrophysiology
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February 22, 2001;
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[Abstract]
[Full Text]
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T. Opitz, S. Y. Grooms, M. V. L. Bennett, and R. S. Zukin
Remodeling of alpha -amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit composition in hippocampal neurons after global ischemia
PNAS,
November 21, 2000;
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[Abstract]
[Full Text]
[PDF]
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D. Oertel, R. Bal, S. M. Gardner, P. H. Smith, and P. X. Joris
Detection of synchrony in the activity of auditory nerve fibers by octopus cells of the mammalian cochlear nucleus
PNAS,
October 24, 2000;
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[Abstract]
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W. Vandenberghe, E. C. Ihle, D. K. Patneau, W. Robberecht, and J. R. Brorson
AMPA Receptor Current Density, Not Desensitization, Predicts Selective Motoneuron Vulnerability
J. Neurosci.,
October 1, 2000;
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[Abstract]
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T. C. Smith, L.-Y. Wang, and J. R. Howe
Heterogeneous Conductance Levels of Native AMPA Receptors
J. Neurosci.,
March 15, 2000;
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[Abstract]
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M. J Gunthorpe, J. A Peters, C. H Gill, J. J Lambert, and S. C R Lummis
The 4'lysine in the putative channel lining domain affects desensitization but not the single-channel conductance of recombinant homomeric 5-HT3A receptors
J. Physiol.,
January 15, 2000;
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[Abstract]
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T. G. Banke, D. Bowie, H.-K. Lee, R. L. Huganir, A. Schousboe, and S. F. Traynelis
Control of GluR1 AMPA Receptor Function by cAMP-Dependent Protein Kinase
J. Neurosci.,
January 1, 2000;
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[Abstract]
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J. R. Brorson, Z. Zhang, and W. Vandenberghe
Ca2+ Permeation of AMPA Receptors in Cerebellar Neurons Expressing Glu Receptor 2
J. Neurosci.,
November 1, 1999;
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[Abstract]
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V. A Panchenko, C. R Glasser, K. M Partin, and M. L Mayer
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J. Physiol.,
October 15, 1999;
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[Abstract]
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A. L. Carvalho, K. Kameyama, and R. L. Huganir
Characterization of Phosphorylation Sites on the Glutamate Receptor 4 Subunit of the AMPA Receptors
J. Neurosci.,
June 15, 1999;
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[Abstract]
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W. D. Leuschner and W. Hoch
Subtype-specific Assembly of alpha -Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor Subunits Is Mediated by Their N-terminal Domains
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[Abstract]
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V. Derkach, A. Barria, and T. R. Soderling
Ca2+/calmodulin-kinase II enhances channel conductance of alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors
PNAS,
March 16, 1999;
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3269 - 3274.
[Abstract]
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R. Dingledine, K. Borges, D. Bowie, and S. F. Traynelis
The Glutamate Receptor Ion Channels
Pharmacol. Rev.,
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[Abstract]
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D. Bowie, G. D. Lange, and M. L. Mayer
Activity-Dependent Modulation of Glutamate Receptors by Polyamines
J. Neurosci.,
October 15, 1998;
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[Abstract]
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S. J. Myers, J. Peters, Y. Huang, M. B. Comer, F. Barthel, and R. Dingledine
Transcriptional Regulation of the GluR2 Gene: Neural-Specific Expression, Multiple Promoters, and Regulatory Elements
J. Neurosci.,
September 1, 1998;
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[Abstract]
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K. E Pemberton, S. M Belcher, J. A Ripellino, and J. R Howe
High-affinity kainate-type ion channels in rat cerebellar granule cells
J. Physiol.,
July 15, 1998;
510(2):
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[Abstract]
[Full Text]
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C. Rosenmund, Y. Stern-Bach, and C. F. Stevens
The Tetrameric Structure of a Glutamate Receptor Channel
Science,
June 5, 1998;
280(5369):
1596 - 1599.
[Abstract]
[Full Text]
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M. A. Varney, S. P. Rao, C. Jachec, C. Deal, S. D. Hess, L. P. Daggett, F.-F. Lin, E. C. Johnson, and G. Veliçelebi
Pharmacological Characterization of the Human Ionotropic Glutamate Receptor Subtype GluR3 Stably Expressed in Mammalian Cells
J. Pharmacol. Exp. Ther.,
April 1, 1998;
285(1):
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[Abstract]
[Full Text]
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J. D. Clements, A. Feltz, Y. Sahara, and G. L. Westbrook
Activation Kinetics of AMPA Receptor Channels Reveal the Number of Functional Agonist Binding Sites
J. Neurosci.,
January 1, 1998;
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[Abstract]
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M. S. Washburn, M. Numberger, S. Zhang, and R. Dingledine
Differential Dependence on GluR2 Expression of Three Characteristic Features of AMPA Receptors
J. Neurosci.,
December 15, 1997;
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[Abstract]
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H. S. Ying, J. H. Weishaupt, M. Grabb, L. M. T. Canzoniero, S. L. Sensi, C. T. Sheline, H. Monyer, and D. W. Choi
Sublethal Oxygen-Glucose Deprivation Alters Hippocampal Neuronal AMPA Receptor Expression and Vulnerability to Kainate-Induced Death
J. Neurosci.,
December 15, 1997;
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[Abstract]
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Y. Sahara, N. Noro, Y. Iida, K. Soma, and Y. Nakamura
Glutamate Receptor Subunits GluR5 and KA-2 Are Coexpressed in Rat Trigeminal Ganglion Neurons
J. Neurosci.,
September 1, 1997;
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[Abstract]
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M. C. Angulo, B. Lambolez, E. Audinat, S. Hestrin, and J. Rossier
Subunit Composition, Kinetic, and Permeation Properties of AMPA Receptors in Single Neocortical Nonpyramidal Cells
J. Neurosci.,
September 1, 1997;
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[Abstract]
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M. Sekiguchi, M. W. Fleck, M. L. Mayer, J. Takeo, Y. Chiba, S. Yamashita, and K. Wada
A Novel Allosteric Potentiator of AMPA Receptors: 4-[2-(Phenylsulfonylamino)ethylthio]-2,6-Difluoro-Phenoxyacetamide
J. Neurosci.,
August 1, 1997;
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[Abstract]
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L.-J. Chew, M. W. Fleck, P. Wright, S. E. Scherer, M. L. Mayer, and V. Gallo
Growth Factor-Induced Transcription of GluR1 Increases Functional AMPA Receptor Density in Glial Progenitor Cells
J. Neurosci.,
January 1, 1997;
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[Abstract]
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P. Golshani, X.-B. Liu, and E. G. Jones
Differences in quantal amplitude reflect GluR4- subunit number at corticothalamic synapses on two populations of thalamic neurons
PNAS,
March 27, 2001;
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[Abstract]
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H. Tanaka, A. Calderone, T. Jover, S. Y. Grooms, H. Yokota, R. S. Zukin, and M. V. L. Bennett
Ischemic preconditioning acts upstream of GluR2 down-regulation to afford neuroprotection in the hippocampal CA1
PNAS,
February 19, 2002;
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[Abstract]
[Full Text]
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