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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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