A novel role for calcium-independent phospholipase A in alpha-amino-3-hydroxy-5-methylisoxazole-propionate receptor regulation during long-term potentiation.
A considerable body of evidence indicates that phospholipase A(2) (PLA(2)) enzymes participate in long-term potentiation (LTP) of excitatory synaptic transmission. In the present study, we have undertaken experiments to identify which calcium-independent isoform of PLA(2) is involved in synaptic plasticity and to determine whether calcium-independent PLA(2) (iPLA(2)) contributes to post-synaptic processes of LTP. Using field recordings from rat CA1 hippocampal slices, we found that theta-burst stimulation (TBS)-induced LTP of field excitatory post-synaptic potentials (fEPSPs) was abolished by the iPLA(2) inhibitor bromoenol lactone (BEL) but not by the Ca(2+)-dependent PLA(2) inhibitor arachidonyl trifluoromethyl ketone (AACOCF(3)). The ionic currents generated during TBS were not affected during iPLA(2) inhibition as BEL by itself had no effect on the magnitude of facilitation during burst responses. In addition, (R)-BEL, an enantioselective inhibitor of iPLA(2)gamma, precluded TBS-induced LTP, an action that was not replicated by the iPLA(2)beta inhibitors (S)-BEL and methyl arachidonyl fluorophosphonate. (R)-BEL was, however, ineffective on pre-established LTP. Finally, BEL also prevented the potentiation of fEPSPs elicited by brief exposure to 50 microM N-methyl-d-aspartate, as well as the associated up-regulation of alpha-amino-3-hydroxy-5-methylisoxazole-propionate (AMPA) receptor GluR1 subunit levels and the increase of (3)H-AMPA binding in crude synaptic fractions. Collectively, these results unravel a new role for iPLA(2)gamma in LTP, which appears to favor the insertion of AMPA receptors at post-synaptic membranes.
Martel
Marc-André
MA
Département de chimie-biologie, Université du Québec à Trois-Rivières, 3351 boulevard des Forges, C.P. 500, Trois-Rivières, Québec, Canada G9A 5H7.
Patenaude
Christian
C
Ménard
Caroline
C
Alaux
Stéphanie
S
Cummings
Brian S
BS
Massicotte
Guy
G
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D047468:Immunoprecipitation / Q000379:methods; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D016202:N-Methylaspartate / Q000493:pharmacokinetics; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D063065:Organophosphonates / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000502:physiology; D011753:Pyrones / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000493:pharmacokinetics
D001095:Arachidonic Acids; D002118:Calcium; D016202:N-Methylaspartate; D009281:Naphthalenes; D063065:Organophosphonates; D010726:Phosphodiesterase Inhibitors; D010741:Phospholipases A; D020033:Protein Isoforms; D011753:Pyrones; D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C104810:methyl arachidonylfluorophosphonate; C081565:arachidonyltrifluoromethane; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one