title: Myricetin reduces voltage activated potassium channel currents in DRG neurons by a p38 dependent mechanism.
abstract: 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 (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 I(K(V)) isolated. I(K(V)) were concentration-dependently reduced by myricetin (1-75μM myricetin; reduction range 18-78%) with no voltage dependency (-80 to +60mV). The reduction of I(K(V)) was enhanced by blocking p38 with the p38 inhibitor SB203580 (40±20% without SB203580 vs. 62±5% with 5μM SB203580 or 83±7% with 10μM SB203580), but abolished by activation of p38 using anisomycin (40±20% without anisomycin vs. 0.73±17% with 5μM anisomycin). We conclude that myricetin reduces I(K(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.
authors.affiliation: Department of Neurology, University of Duisburg-Essen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Hagenacker
authors.forename: Imke
authors.initials: I
authors.lastname: Hillebrand
authors.forename: Dietrich
authors.initials: D
authors.lastname: Büsselberg
authors.forename: Maria
authors.initials: M
authors.lastname: Schäfers
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology*; D007093:Imidazoles / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines; C040015:myricetin; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580