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

  title={Control of kinetic properties of GluR2 flop AMPA‐type channels: impact of R/G nuclear editing},
  author={Klaus Krampfl and Friedrich Schlesinger and Antje Z{\"o}rner and Martin Kappler and Reinhard Dengler and Johannes Bufler},
  journal={European Journal of Neuroscience},
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… 
R/G editing in GluA2Rflop modulates the functional difference between GluA1 flip and flop variants in GluA1/2R heteromeric channels
R/G editing via GluA2R serve as a regulatory mechanism to modulate the function of Glu a2R-containing, native receptors involved in fast excitatory synaptic transmission, as well as modulating the channel properties in both homomeric and complex channel forms.
Kinetic properties of human AMPA‐type glutamate receptors expressed in HEK293 cells
AMPA‐type glutamate receptors (AMPAR) display a high variability in functional properties, which determine the time course of excitatory postsynaptic potentials. They are assembled as tetramers of
Two mechanisms of action of the adamantane derivative IEM‐1460 at human AMPA‐type glutamate receptors
The extent of current inhibition as well as the time constant of current decay upon addition of the blocker to the test solution were dependent on agonist concentration; this strongly points to an additional competitive‐like block mechanism of IEM‐1460 at human AMPA‐type GluR channels.
Desensitization and resensitization are independently regulated in human recombinant GluR subunit coassemblies
It was found that τD had intermediate values depending on the amount of cDNA of the respective subunit at all heteromeric and homomeric GluR channels tested, and τrec had values close to that of fast resensitizing GLUR2 flip channels, even in the case of an abundance of GluGluR1 cDNA.
Kinetic analysis of recombinant mammalian α1 and α1β glycine receptor channels
To analyze the influence of the β-subunit on the kinetic properties of GlyR channel currents, α1-sub units and α1β-subunits were transiently expressed in HEK 293 cells and resulted in a significantly lower EC50 and a reduced slope of the dose–response curve of glycine compared with expression of α1–subunits alone.
Glutamate receptor RNA editing in health and disease
Overall, these data indicate that a highly regulated process of glutamate receptor editing is of key importance in the proper function of neuronal cells and in their ability to adapt and modulate synaptic function.
Modulation of dendritic AMPA receptor mRNA trafficking by RNA splicing and editing
The data show that post-transcriptional regulations such as RNA splicing, editing and trafficking might be mutually coordinated and that the localization of different AMPAR isoforms in dendrites might play a functional role in the regulation of neuronal transmission.
The Biochemistry, Ultrastructure, and Subunit Assembly Mechanism of AMPA Receptors
  • T. Nakagawa
  • Biology, Chemistry
    Molecular Neurobiology
  • 2010
The current ultrastructural data on the receptors and the receptor-expressing stable cell lines that were developed during the course of these studies are useful resources for high throughput drug screening and further drug designing and are getting closer to understanding the precise mechanisms of AMPA-R-mediated synaptic plasticity.
Involvement of AMPA Receptor and Its Flip and Flop Isoforms in Retinal Ganglion Cell Death Following Oxygen/Glucose Deprivation.
Following oxidative injury, RGCs become more susceptible to AMPAR-mediated excitotoxicity.


Regulation of Kinetic Properties of GluR2 AMPA Receptor Channels by Alternative Splicing
The slower desensitization kinetics and larger steady-state current responses in the flip variant were also observed in heteromeric receptors assembled from GluR 2Q/GluR2R, and desensItization occurred much more prominently in the flop variant in the recombinant GLUR2 receptor channels.
Control of kinetic properties of AMPA receptor channels by nuclear RNA editing.
Site-selective nuclear RNA editing controls the calcium permeability of AMPA receptor channels, and RNA editing at a second site is shown here to affect the kinetic aspects of these channels in rat brain.
Single-Channel Properties of Recombinant AMPA Receptors Depend on RNA Editing, Splice Variation, and Subunit Composition
It is suggested that the single-channel conductance of certain recombinant AMPA receptors may be determined by the expression of edited GluR2 subunits in neurons.
Structural determinants of ion flow through recombinant glutamate receptor channels
The properties of heteromeric wild-type and mutant GluRs revealed that the dominance of GluR-B is due to the arginine residue in the TM2 region, and the steady-state current-voltage relations of glutamate- and kainate-induced currents through homomeric channels fell into two classes.
Control of rat GluR6 glutamate receptor open probability by protein kinase A and calcineurin
It is concluded that the binding of glutamate to homomeric GluR6 receptors is associated with a high probability of channel opening, which is under the control of two signalling systems that are known to be co‐localized at the neuronal membrane.
Control of GluR1 AMPA Receptor Function by cAMP-Dependent Protein Kinase
It is suggested that AMPA receptor peak response open probability can be increased by PKA through phosphorylation of GluR1 Ser845.
AMPA Receptor Flip/Flop Mutants Affecting Deactivation, Desensitization, and Modulation by Cyclothiazide, Aniracetam, and Thiocyanate
The experiments demonstrate for the first time the functional importance of residue 750 in regulating intrinsic channel-gating kinetics and emphasize the biological significance of alternative splicing in the M3–M4 extracellular loop.
A molecular determinant for submillisecond desensitization in glutamate receptors.
These findings suggest that rapid desensitization of AMPA receptors can be regulated by the expression and alternative splicing of GluR-D gene transcripts.