Journal
SYNAPSE
Volume 64, Issue 5, Pages 390-396Publisher
WILEY
DOI: 10.1002/syn.20738
Keywords
osthole; imperatorin; glutamate exocytotic machinery; CaMKII; synapsin I; hippocampal nerve terminals
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Funding
- National Science Council of Taiwan, Republic of China [NSC 96-2628-B-030-001-MY3]
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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 KCI-evoked FMI-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. Synapse 64:390-396, 2010. (C) 2009 Wiley-Liss, Inc.
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