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AMPA receptor function is altered in GLUR2-deficient mice
1Neuroscience Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285-0510, USA.
Journal of Molecular Neuroscience : MN
|October 23, 2001
Summary
Mice lacking the GluR2 subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors survive due to slower recovery from desensitization. This mechanism reduces calcium influx, preventing toxicity in these GluR2 (-/-) mice.
Area of Science:
- Neuroscience
- Molecular Biology
- Biophysics
Background:
- The GluR2 subunit of AMPA receptors is critical for controlling calcium permeability and receptor biophysics.
- Genetic manipulation preventing GluR2 editing leads to early mortality from calcium toxicity, while gene disruption is not lethal.
Purpose of the Study:
- To investigate the mechanisms enabling survival in GluR2 (-/-) mice with highly calcium-permeable AMPA receptors.
- To understand how these mice tolerate increased calcium influx.
Main Methods:
- Whole-cell patch-clamp recordings were used to analyze AMPA receptor function in cortical pyramidal cells.
- Analysis focused on the kinetics of receptor desensitization and recovery.
- RNA editing and alternative splicing of related subunits were examined.
Main Results:
- AMPA receptors in GluR2 (-/-) mice exhibited significantly slower recovery from desensitization (109.8 ms) compared to wild-type mice (54.4 ms).
- This slower recovery is predicted to decrease calcium influx during neuronal activity.
- No significant changes in RNA editing or alternative splicing of GluR1, 3, or 4 subunits were observed.
Conclusions:
- Slower recovery from desensitization is a key factor contributing to the survival of GluR2 (-/-) mice.
- This adaptation mitigates the potentially toxic effects of enhanced calcium permeability through AMPA receptors.
