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GluR3 flip and flop: differences in channel opening kinetics.
Weimin Pei1, Zhen Huang, Li Niu
1Department of Chemistry and Center for Neuroscience Research, University at Albany, SUNY, Albany, New York 12222, USA.
Biochemistry
|January 30, 2007
Summary
Alternative splicing of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, specifically GluR3, impacts channel closing rates. The flip variant stabilizes open channel conformation, unlike the flop variant.
Area of Science:
- Neuroscience
- Molecular Biology
- Biophysics
Background:
- Alternative splicing of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors generates functional diversity.
- The impact of alternative splicing on the microsecond kinetics of AMPA receptor channel opening remains largely uncharacterized.
Purpose of the Study:
- To investigate how alternative splicing affects the channel gating kinetics of GluR3 AMPA receptors.
- To determine whether the flip-flop variants of GluR3 influence channel opening, closing, or ligand binding rates.
Main Methods:
- Utilized laser-pulse photolysis combined with whole-cell recording techniques.
- Characterized the channel opening rate process for GluR3flip and GluR3flop variants.
Main Results:
- Alternative splicing in GluR3 receptors regulates channel closing rates, not opening rates or glutamate binding affinity.
- The GluR3flop variant exhibits a nearly 4-fold faster channel closing rate compared to the GluR3flip variant.
- Kinetic analysis suggests GluR3 flip isoforms are more similar to GluR2 and GluR4 than GluR1.
Conclusions:
- The flip-flop sequence module in AMPA receptors likely stabilizes the open channel conformation.
- Alternative splicing plays a critical role in modulating the dynamic properties of AMPA receptor channels.
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