Myricetin reduces voltage activated potassium channel currents in DRG neurons by a p38 dependent mechanism

Myricetin is a naturally occurring flavonoid known for its anti-neoplasm anti-oxidant and anti-inflammatory effects Currently potential analgesic effects are proposed for several animal models of acute and chronic pain Pilot studies show a flavonoid-induced modulation of intracellular mitogen-activated protein kinases (MAPK) as p38 and interactions with voltage activated potassium channel currents (I-K(v)) The aim of this study was to investigate the underlying modulation of I-K(v) and the influence of MAPK phosphorylation in an in vitro cell model Whole cell patch-clamp recordings of rat dorsal root ganglion neurons were performed and IK(v) isolated I-K(V) were concentration-dependently reduced by myricetin (1-75 mu M myricetin reduction range 18-78%) with no voltage dependency (-80 to +60 mV) The reduction of I-K(V) was enhanced by blocking p38 with the p38 inhibitor SB203580 (40 +/- 20% without SB203580 vs 62 +/- 5% with 5 mu M SB203580 or 83 +/- 7% with 10 mu M SB203580) but abolished by activation of p38 using anisomycin (40 +/- 20% without anisomycm vs 0 73 +/- 17% with 5 mu M anisomycin) We conclude that myricetin reduces IK(v) by p38 dependent mechanisms in sensory neurons Since a reduction of I-K(V) rather increases neuronal excitability it is unlikely that this effect of myricetin contributes to its analgesic effects (C) 2010 Elsevier Inc All rights reserved