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DCP‐LA stimulates AMPA receptor exocytosis through CaMKII activation due to PP‐1 inhibition
Author(s) -
Kanno Takeshi,
Yaguchi Takahiro,
Nagata Tetsu,
Tanaka Akito,
Nishizaki Tomoyuki
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21838
Subject(s) - ampa receptor , long term potentiation , phenylarsine oxide , exocytosis , chemistry , neurotransmission , kainate receptor , receptor , glutamate receptor , microbiology and biotechnology , biochemistry , biology , membrane
The linoleic acid derivative 8‐[2‐(2‐pentyl‐cyclopropylmethyl)‐cyclopropyl]‐octanoic acid (DCP‐LA) activated Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII) by inhibiting protein phosphatase‐1 (PP‐1). DCP‐LA induced a transient huge facilitation of synaptic transmission monitored from the CA1 region of rat hippocampal slices, which was largely inhibited by the CaMKII inhibitor KN‐93. DCP‐LA potentiated kainate‐evoked whole‐cell membrane currents for Xenopus oocytes expressing α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptors composed of the GluR1, GluR3, GluR1/GluR2, GluR1/GluR3, and GluR1/GluR2/GluR3 subunits, and the potentiation was significantly inhibited by KN‐93. A similar potentiation was still found with mutant GluR1 (S831A) receptor lacking CaMKII phosphorylation site. The GluR1 and GluR2 subunits formed AMPA receptors in the rat hippocampus, and DCP‐LA increased expression of both the subunits on the plasma membrane. The DCP‐LA action was blocked by KN‐93 and the exocytosis inhibitor botulinum toxin type A, but not by the endocytosis inhibitor phenylarsine oxide. DCP‐LA, thus, appears to activate CaMKII through PP‐1 inhibition, that stimulates AMPA receptor exocytosis to increase expression of the receptors on the plasma membrane, responsible for potentiate AMPA receptor responses and facilitation of hippocampal synaptic transmission. J. Cell. Physiol. 221: 183–188, 2009. © 2009 Wiley‐Liss, Inc