London Pain Consortium.
Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons
Version of Record online: 28 APR 2005
European Journal of Neuroscience
Volume 21, Issue 7, pages 1785–1797, April 2005
How to Cite
Pezet, S., Spyropoulos, A., Williams, R. J. and McMahon, S. B. (2005), Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons. European Journal of Neuroscience, 21: 1785–1797. doi: 10.1111/j.1460-9568.2005.04011.x
- Issue online: 28 APR 2005
- Version of Record online: 28 APR 2005
- Received 13 August 2004, revised 7 January 2005, accepted 14 January 2005
The serine/threonine kinase Akt/PKB has been implicated in cell survival signalling in many cell types, including the dorsal root ganglion (DRG). However, little is known about its role in physiological and pathophysiological conditions in the adult sensory and nociceptive system. In this study, we show that in naïve animals almost all cells express Akt but only a subset of small-diameter neurons expresses a high level of phospho-Akt (p-Akt Ser 473). Activation of peripheral nociceptors in vivo using intraplantar injections of capsaicin in anaesthetized rats induced a rapid onset and time-dependent increase in p-Akt Ser 473 in small- and medium-sized DRG, predominantly TRPV1-positive neurons. In addition, electrical stimulation of ‘A and C’ fibres in the sciatic nerve induced an increase in the cytoplasmic staining of p-Akt Ser 473 in small- and medium-size DRG neurons. Blocking neuronal activity in the sciatic nerve using tetrodotoxin reduced the basal level of p-Akt Ser 473. Cultured DRG neurons confirmed that phosphorylation of Akt in different cellular compartments is triggered by depolarization or receptor activation, and suggested that this effect is mediated in part by phosphatidylinositol 3-kinase. Our results show that p-Akt Ser 473 is a marker of nociceptor activation and suggest a novel role for Akt in the transduction of intracellular signals in adult DRG neurons.