Osthole or imperatorin-mediated facilitation of glutamate release is associated with a synaptic vesicle mobilization in rat hippocampal glutamatergic nerve endings

Tzu Yu Lin, Cheng Wei Lu, Wei Jan Huang, Su Jane Wang

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12 Citations (Scopus)

Abstract

Osthole and imperatorin, two active compounds of Cnidium monnieri (L.) Cusson, have previously been shown to facilitate depolarization-evoked glutamate release from rat hippocampal nerve terminals by increasing voltage-dependent Ca2+ entry. In this study, we further investigated whether osthole and imperatorin possess an action at the exocytotic machinery itself, downstream of a Ca2+ influx. Our data showed that ionomycin-induced glutamate release and KCl-evoked FM1-43 release were facilitated by osthole and imperatorin, suggesting that some steps after Ca2+ entry are regulated by these two compounds. Consistent with this, osthole or imperatorin-mediated facilitation of ionomycin-induced glutamate release was occluded by cytochalasin D that inhibits actin polymerization, implying that the disassembly of cytoskeleton is involved. In addition, the facilitatory action of osthole or imperatorin on ionomycin-induced glutamate release was attenuated by the Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor KN62. Furthermore, Western blotting analysis further showed that osthole or imperatorin significantly increased ionomycin-induced phosphorylation of CaMKII and synapsin I, the main presynaptic target of CaMKII. These results suggest, therefore, that osthole or imperatorin-mediated facilitation of glutamate release involves modulation of downstream events controlling synaptic vesicle recruitment and exocytosis, possibly through an increase of CaMKII activation and synapsin I phosphorylation, thereby increasing synaptic vesicle availability for exocytosis.

Original languageEnglish
Pages (from-to)390-396
Number of pages7
JournalSynapse
Volume64
Issue number5
DOIs
Publication statusPublished - May 2010

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Keywords

  • CaMKII
  • Glutamate exocytotic machinery
  • Hippocampal nerve terminals
  • Imperatorin
  • Osthole
  • Synapsin I

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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