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Calcium‐independent phospholipase A 2 influences AMPA‐mediated toxicity of hippocampal slices by regulating the GluR1 subunit in synaptic membranes
Author(s) -
Ménard Caroline,
Chartier Émilie,
Patenaude Christian,
Robinson Pierre,
Cyr Michel,
Baudry Michel,
Massicotte Guy
Publication year - 2007
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20343
Subject(s) - ampa receptor , hippocampal formation , neuroscience , chemistry , protein subunit , calcium , glutamate receptor , biology , biochemistry , receptor , gene , organic chemistry
Abstract We have recently documented that phosphorylation of the GluR1 subunit of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐propionate (AMPA) glutamate receptors is influenced by calcium‐independent forms of phospholipase A 2 (iPLA 2 ) activity in the brain. Given the importance of GluR1 subunit phosphorylation in the control of AMPA receptor delivery to synaptic membranes, we tested the influence of iPLA 2 activity on AMPA receptor distribution between neuronal compartments, using organotypic cultured hippocampal slices. In agreement with earlier reports, the iPLA 2 inhibitor bromoenol lactone (BEL) markedly enhanced the phosphorylation of the GluR1 subunit at both Ser831 and Ser845 residues. GluR1 subunit phosphorylation levels were selectively increased by ( R )‐BEL, an enantio‐selective inhibitor of iPLA 2 γ, but not by ( S )‐BEL, an iPLA 2 β inhibitor. The iPLA 2 γ inhibitor R‐BEL also promoted the insertion of new GluR1 subunits into synaptic membranes and exacerbated AMPA‐mediated cell death in the CA1 region of the hippocampus. The latter effect was selectively abolished by IEM 1460 and philanthotoxin‐433, two antagonists specific for AMPA receptors lacking GluR2 subunits. These results provide evidence that iPLA 2 γ‐related regulation of AMPA receptor GluR1 subunit phosphorylation could represent an important mechanism modulating hippocampal cell death induced by AMPA receptor overstimulation. © 2007 Wiley‐Liss, Inc.