Glycine-induced long-term potentiation is associated with structural and functional modifications of α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptors
Autor: | Wael Musleh, Shahriar S. Yaghoubi, Xiaoning Bi, Michel Baudry, Georges Tocco |
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Rok vydání: | 1997 |
Předmět: |
Multidisciplinary
biology Chemistry musculoskeletal neural and ocular physiology Long-Term Potentiation Glycine Long-term potentiation Calpain AMPA receptor Biological Sciences Hippocampus Rats Rats Sprague-Dawley Organ Culture Techniques nervous system Biochemistry biology.protein LTP induction Biophysics Animals Spectrin Receptors AMPA Receptor Long-term depression |
Zdroj: | Proceedings of the National Academy of Sciences. 94:9451-9456 |
ISSN: | 1091-6490 0027-8424 |
DOI: | 10.1073/pnas.94.17.9451 |
Popis: | Global long-term potentiation (LTP) was induced in organotypic hippocampal slice cultures by a brief application of 10 mM glycine. Glycine-induced LTP was occluded by previous theta burst stimulation-induced potentiation, indicating that both phenomena share similar cellular processes. Glycine-induced LTP was associated with increased [ 3 H]α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) binding in membrane fractions as well as increased amount of a selective spectrin breakdown product generated by calpain-mediated spectrin proteolysis. Antibodies against the C-terminal (C-Ab) and N-terminal (N-Ab) domains of GluR1 subunits were used to evaluate structural changes in AMPA receptor properties resulting from glycine-induced LTP. No quantitative or qualitative changes were observed in Western blots from membrane fractions prepared from glycine-treated slices with C-Ab. In contrast, Western blots stained with N-Ab revealed the formation of a 98-kDa species of GluR1 subunits as well as an increased amount of immunoreactivity after glycine-induced LTP. The amount of spectrin breakdown product was positively correlated with the amount of the 98-kDa species of GluR1 after glycine treatment. Functional modifications of AMPA receptors were evaluated by determining changes in the effect of pressure-applied AMPA on synaptic responses before and after glycine-induced LTP. Glycine treatment produced a significant increase in AMPA receptor function after potentiation that correlated with the degree of potentiation. The results indicate that LTP induction produces calpain activation, truncation of the C-Ab domain of GluR1 subunits of AMPA receptors, and increased AMPA receptor function. They also suggest that insertion of new receptors takes place after LTP induction. |
Databáze: | OpenAIRE |
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