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Long‐term potentiation requires activation of calcium‐independent phospholipase A 2
Author(s) -
Matthew J. Wolf,
Yukitoshi Izumi,
Charles F. Zorumski,
Richard W. Gross
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01371-7
Subject(s) - long term potentiation , excitatory postsynaptic potential , chemistry , phospholipase , arachidonic acid , phospholipase a2 , calcium , tetanic stimulation , phospholipase a , stimulation , biochemistry , biophysics , endocrinology , biology , enzyme , receptor , organic chemistry
The predominant phospholipase activity present in rat hippocampus is a calcium‐independent phospholipase A 2 (302.9 ± 19.8 pmol/mg·min for calcium‐independent phospholipase A 2 activity vs. 14.6 ± 1.0 pmol/mg·min for calcium‐dependent phospholipase A 2 activity). This calcium‐independent phospholipase A 2 is exquisitely sensitive to inhibition by the mechanism‐based inhibitor, ( E )‐6‐(bromomethylene)‐tetrahydro‐3‐(1‐naphthalenyl)‐2H‐pyran ‐2‐one (BEL). Moreover, treatment of hippocampal slices with BEL prior to tetanic stimulation prevents the induction of LTP (40.8 ± 5.6% increase in excitatory postsynaptic potential (EPSP) slope for control slices ( n = 6) vs. 5.8 ± 8.5% increase in EPSP slope for BEL‐treated slices ( n = 8)). Importantly, LTP can be induced following mechanism‐based inhibition of phospholipase A 2 by providing the end product of the phospholipase A 2 reaction, arachidonic acid, during the application of tetanic stimulation. Furthermore, the induction of LTP after treatment with BEL is dependent on the stereoelectronic configuration of the fatty acid provided since eicosa‐5,8,11‐trienoic acid, but not eicosa‐8,11,14‐trienoic acid, rescues LTP after BEL treatment (37.6 ± 16.1% increase in EPSP slope for eicosa‐5,8,11‐trienoic acid vs. −3.7 ± 5.2% increase in EPSP slope for eicosa‐8,11,14‐trienoic acid). Collectively, these results provide the first demonstration of the essential role of calcium‐independent phospholipase A 2 in synaptic plasticity.