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[PKC.sub. [epsilon]] phosphorylation of the sodium channel [Na.sub.v] 1.8 increases channel function and produces mechanical hyperalgesia in mice
Ist Teil von
The Journal of clinical investigation, 2012-04, Vol.122 (4), p.1306
Ort / Verlag
American Society for Clinical Investigation
Erscheinungsjahr
2012
Quelle
EZB Free E-Journals
Beschreibungen/Notizen
Mechanical hyperalgesia is a common and potentially disabling complication of many inflammatory and neuropathic conditions. Activation of the enzyme PKC ζ in primary afferent nociceptors is a major mechanism that underlies mechanical hyperalgesia, but the PKC ζ substrates involved downstream are not known. Here, we report that in a proteomic screen we identified the [Na.sub.V] 1.8 sodium channel, which is selectively expressed in nociceptors, as a PKC ζ substrate. PKC ζ -mediated phosphorylation increased [Na.sub.V] 1.8 currents, lowered the threshold voltage for activation, and produced a depolarizing shift in inactivation in wild-type--but not in PKC ζ -null - sensory neurons. PKC ζ phosphorylated NaV1.8 at S1452, and alanine substitution at this site