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Evidence-Based Complementary and Alternative Medicine
Volume 2012 (2012), Article ID 758097, 10 pages
http://dx.doi.org/10.1155/2012/758097
Research Article

Flavonoid Myricetin Modulates Receptor Activity through Activation of Channels and CaMK-II Pathway

1Epithelial Cell Biology Research Centre, The Chinese University of Hong Kong, Hong Kong
2Department of Physiology, Medical College Qingdao University, Qingdao, China
3Laboratory Animal Services Centre, The Chinese University of Hong Kong, Hong Kong
4Department of Physiology, School of Basic Medical Sciences, Jilin University, Changchun, China
5School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong

Received 20 June 2012; Revised 31 July 2012; Accepted 10 August 2012

Academic Editor: Ke Ren

Copyright © 2012 Xiao Hu Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The flavonoid myricetin is found in several sedative herbs, for example, the St. John's Wort, but its influence on sedation and its possible mechanism of action are unknown. Using patch-clamp technique on a brain slice preparation, the present study found that myricetin promoted GABAergic activity in the neurons of hypothalamic paraventricular nucleus (PVN) by increasing the decay time and frequency of the inhibitory currents mediated by receptor. This effect of myricetin was not blocked by the receptor benzodiazepine- (BZ-) binding site antagonist flumazenil, but by KN-62, a specific inhibitor of the Ca2+/calmodulin-stimulated protein kinase II (CaMK-II). Patch clamp and live Ca2+ imaging studies found that myricetin could increase Ca2+ current and intracellular Ca2+ concentration, respectively, via T- and L-type Ca2+ channels in rat PVN neurons and hypothalamic primary culture neurons. Immunofluorescence staining showed increased phosphorylation of CaMK-II after myricetin incubation in primary culture of rat hypothalamic neurons, and the myricetin-induced CaMK-II phosphorylation was further confirmed by Western blotting in PC-12 cells. The present results suggest that myricetin enhances receptor activity via calcium channel/CaMK-II dependent mechanism, which is distinctively different from that of most existing BZ-binding site agonists of receptor.