Control of kinetic properties of GluR2 flop AMPA-type channels: impact of R/G nuclear editing

The GluR2 flop subunit of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)‐type glutamate receptors greatly determines calcium permeability and kinetic properties of heteromeric AMPA subunit assemblies. Post‐transcriptional editing of this subunit at the Q/R/N site controls calcium permea...

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Bibliographic Details
Published in:The European journal of neuroscience 2002-01, Vol.15 (1), p.51-62
Main Authors: Krampfl, Klaus, Schlesinger, Friedrich, Zörner, Antje, Kappler, Martin, Dengler, Reinhard, Bufler, Johannes
Format: Article
Language:English
Subjects:
Algorithms
Biotransformation
Cell Line
Cell Nucleus - genetics
Cell Nucleus - metabolism
Computer Simulation
desensitization
Electrophysiology
Hippocampus - metabolism
human AMPA-type receptors
Humans
Ion Channel Gating - genetics
Kinetics
nonstationary noise analysis
Patch-Clamp Techniques
Protein Processing, Post-Translational - genetics
Receptors, AMPA - genetics
Receptors, AMPA - metabolism
recovery from desensitization
RNA Editing - genetics
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Summary:The GluR2 flop subunit of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)‐type glutamate receptors greatly determines calcium permeability and kinetic properties of heteromeric AMPA subunit assemblies. Post‐transcriptional editing of this subunit at the Q/R/N site controls calcium permeability whereas editing at the R/G site is involved in the regulation of biophysical properties. We used patch‐clamp techniques with ultrafast solution exchange to examine the kinetics of recombinant human homomeric GluR2 flop channels transiently expressed in HEK293 cells [edited at the R/G site and Q/R/N site (GR), and unedited (RN) and edited (GN) at the R/G site both with asparagine (N) at the Q/R/N site]. The time constant of desensitization after application of 10 mm glutamate was 1.38 ± 0.05 ms (n = 10), 5.53 ± 0.57 ms (n = 7) and 1.33 ± 0.06 ms (n = 12) for the GluR2 flop GR, RN and GN channels, respectively. The time constant of resensitization was 75 ms for the GluR2 flop RN and 30 ms for the GN channels. The dose‐dependence of the peak current amplitude, kinetics of activation and deactivation, and peak open probability did not differ between RN and GN channels. The study shows that desensitization and resensitization kinetics of homomeric GluR2 flop channels are controlled by a single amino acid exchange (glycine by arginine) at the R/G site. Quantitative analysis by computer simulation using a circular kinetic scheme allows the prediction of the main experimental results.
ISSN:0953-816X
1460-9568
DOI:10.1046/j.0953-816x.2001.01841.x