Arachidonic acid induces a long-lasting facilitation of hippocampal synaptic transmission by modulating PKC activity and nicotinic ACh receptors

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• 作者：Nishizaki ; Tomoyuki ; Nomura ; Tamotsu ; Matsuoka ; Toshiyuki ; Enikolopov ; Grigori ; Sumikawa ; Katumi
• 关键词：Arachidonic acid ; Nicotinic ACh receptor ; Protein kinase C ; Synaptic transmission ; Long-term potentiation ; Hippocampus
• 刊名：Molecular Brain Research
• 出版年：1999
• 出版时间：June 8, 1999
• 年：1999
• 卷：69
• 期：2
• 页码：263-272
• 全文大小：462 K

文摘

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 (α7 and α4β2) 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, α-bungarotoxin and mecamylamine. The facilitation, whereas independent of N-methyl--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.