Flavonoid Myricetin Modulates GABA(A) Receptor Activity through Activation of Ca2+ Channels and CaMK-II Pathway
Publication in refereed journal


Times Cited
Web of Science7WOS source URL (as at 16/10/2020) Click here for the latest count
Altmetrics Information
.

Other information
AbstractThe 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 GABA(A) receptor. This effect of myricetin was not blocked by the GABA(A) 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 GABA(A) receptor activity via calcium channel/CaMK-II dependent mechanism, which is distinctively different from that of most existing BZ-binding site agonists of GABA(A) receptor.
All Author(s) ListZhang XH, Ma ZG, Rowlands DK, Gou YL, Fok KL, Wong HY, Yu MK, Tsang LL, Mu L, Chen L, Yung WH, Chung YW, Zhang BL, Zhao H, Chan HC
Journal nameEvidence-Based Complementary and Alternative Medicine
Detailed descriptionTo ORKTS: doi: 10.1155/2012/758097 (WONG Hau Yan Connie is working at Department of Physiology, CUHK instead of the Epithelial Cell Biology Research C
Year2012
Month1
Day1
PublisherHindawi Publishing Corporation / Oxford University Press (OUP): Policy B
ISSN1741-427X
eISSN1741-4288
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesIntegrative & Complementary Medicine; INTEGRATIVE & COMPLEMENTARY MEDICINE

Last updated on 2020-17-10 at 01:06