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-neoplastic, 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 (IK(V)). The aim of this study was to investigate the underlying modulation of IK(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. IK(V) were concentration-dependently reduced by myricetin (1–75 μM myricetin; reduction range 18–78%) with no voltage dependency (−80 to +60 mV). The reduction of IK(V) was enhanced by blocking p38 with the p38 inhibitor SB203580 (40 ± 20% without SB203580 vs. 62 ± 5% with 5 μM SB203580 or 83 ± 7% with 10 μM SB203580), but abolished by activation of p38 using anisomycin (40 ± 20% without anisomycin vs. 0.73 ± 17% with 5 μM anisomycin).We conclude that myricetin reduces IK(V) by p38 dependent mechanisms in sensory neurons. Since a reduction of IK(V) rather increases neuronal excitability, it is unlikely that this effect of myricetin contributes to its analgesic effects.