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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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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; 19(21): 9149 - 9159.
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J. Physiol.Home page
V. A Panchenko, C. R Glasser, K. M Partin, and M. L Mayer
Amino acid substitutions in the pore of rat glutamate receptors at sites influencing block by polyamines
J. Physiol., October 15, 1999; 520(2): 337 - 357.
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J. Neurosci.Home page
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; 19(12): 4748 - 4754.
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J. Biol. Chem.Home page
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
J. Biol. Chem., June 11, 1999; 274(24): 16907 - 16916.
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Proc. Natl. Acad. Sci. USAHome page
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; 96(6): 3269 - 3274.
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Pharmacol. Rev.Home page
R. Dingledine, K. Borges, D. Bowie, and S. F. Traynelis
The Glutamate Receptor Ion Channels
Pharmacol. Rev., March 1, 1999; 51(1): 7 - 62.
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J. Neurosci.Home page
D. Bowie, G. D. Lange, and M. L. Mayer
Activity-Dependent Modulation of Glutamate Receptors by Polyamines
J. Neurosci., October 15, 1998; 18(20): 8175 - 8185.
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J. Neurosci.Home page
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; 18(17): 6723 - 6739.
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J. Physiol.Home page
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): 401 - 420.
[Abstract] [Full Text] [PDF]


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ScienceHome page
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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J. Pharmacol. Exp. Ther.Home page
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): 358 - 370.
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J. Neurosci.Home page
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; 18(1): 119 - 127.
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J. Neurosci.Home page
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; 17(24): 9393 - 9406.
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J. Neurosci.Home page
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; 17(24): 9536 - 9544.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
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; 17(17): 6611 - 6620.
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J. Neurosci.Home page
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; 17(17): 6685 - 6696.
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J. Neurosci.Home page
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; 17(15): 5760 - 5771.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
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; 17(1): 227 - 240.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
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; 98(7): 4172 - 4177.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
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; 99(4): 2362 - 2367.
[Abstract] [Full Text] [PDF]



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