title: Arachidonic acid induces a long-lasting facilitation of hippocampal synaptic transmission by modulating PKC activity and nicotinic ACh receptors.
abstract: The present study was conducted to understand the effect of arachidonic acid on nicotinic acetylcholine (ACh) receptor-mediated synaptic plasticity. Arachidonic acid persistently (>/=1 h) potentiated currents through neuronal nicotinic ACh receptors (alpha7 and alpha4beta2) expressed in Xenopus oocytes, and the effect was blocked by the selective protein kinase C (PKC) inhibitors, such as GF109203X, PKCI, and co-expressed active PKC inhibitor peptide. This free fatty acid markedly increased nicotine-sensitive glutamate release from hippocampal slices and enhanced the rate of nicotine-sensitive miniature excitatory postsynaptic currents without affecting the amplitude in cultured hippocampal CA1 neurons under the influence of PKC. Furthermore, arachidonic acid induced a long-lasting (>/=3 h) facilitation of hippocampal CA1 synaptic transmission in slices, and the effect was blocked by nicotinic ACh receptor antagonists, alpha-bungarotoxin and mecamylamine. The facilitation, whereas independent of N-methyl-D-aspartate (NMDA) receptors, shares a common mechanism with long-term potentiation (LTP) induced by tetanic stimulation. The results of the present study thus suggest that arachidonic acid sustains enhanced activity of nicotinic ACh receptors by interacting with a PKC pathway, thereby increasing glutamate release from presynaptic terminals, and then leading to an 'LTP-like' facilitation of hippocampal synaptic transmission.
authors.affiliation: Department of Physiology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. tomo@med.kobe-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Nishizaki
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: T
authors.initials: T
authors.lastname: Matsuoka
authors.forename: G
authors.initials: G
authors.lastname: Enikolopov
authors.forename: K
authors.initials: K
authors.lastname: Sumikawa
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D014981:Xenopus
chemical_list: D011978:Receptors, Nicotinic; D016718:Arachidonic Acid; D011493:Protein Kinase C