PubMed 19828806

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Nav1.6

Title: Inhibitor kappaB Kinase beta deficiency in primary nociceptive neurons increases TRP channel sensitivity.

Authors: Vanessa Bockhart, Cristina Elena Constantin, Annett Häussler, Nina Wijnvoord, Maike Kanngiesser, Thekla Myrczek, Geethanjali Pickert, Laura Popp, Jürgen-Markus Sobotzik, Manolis Pasparakis, Rohini Kuner, Gerd Geisslinger, Christian Schultz, Michaela Kress, Irmgard Tegeder

Journal, date & volume: J. Neurosci., 2009 Oct 14 , 29, 12919-29

PubMed link:

Inhibitor kappaB kinase (IKK) regulates the activity of the transcription factor nuclear factor-kappa B that normally protects neurons against excitotoxicity. Constitutively active IKK is enriched at axon initial segments and nodes of Ranvier (NR). We used mice with a Cre-loxP-mediated specific deletion of IKKbeta in sensory neurons of the dorsal root ganglion (SNS-IKKbeta(-/-)) to evaluate whether IKK plays a role in sensory neuron excitability and nociception. We observed increased sensitivity to mechanical, cold, noxious heat and chemical stimulation in SNS-IKKbeta(-/-) mice, with normal proprioceptive and motor functions as revealed by gait analysis. This was associated with increased calcium influx and increased inward currents in small- and medium-sized primary sensory neurons of SNS-IKKbeta(-/-) mice during stimulation with capsaicin or Formalin, specific activators of transient receptor potentials TRPV1 and TRPA1 calcium channels, respectively. In vitro stimulation of saphenous nerve preparations of SNS-IKKbeta(-/-) mice showed increased neuronal excitability of A- and C-fibers but unchanged A- and C-fiber conduction velocities, normal voltage-gated sodium channel currents, and normal accumulation of ankyrin G and the sodium channels Nav1.6 at NR. The results suggest that IKKbeta functions as a negative modulator of sensory neuron excitability, mediated at least in part by modulation of TRP channel sensitivity.