Ankyrin-rich Membrane Spanning Protein as a Novel Modulator of Transient Receptor Potential Vanilloid 1-function in Nociceptive Neurons

Eur J Pain. 2017 Jul;21(6):1072-1086. doi: 10.1002/ejp.1008. Epub 2017 Feb 9.

Abstract

Background: The ion channel TRPV1 is mainly expressed in small diameter dorsal root ganglion (DRG) neurons, which are involved in the sensation of acute noxious thermal and chemical stimuli. Direct modifications of the channel by diverse signalling events have been intensively investigated, but little is known about the composition of modulating macromolecular TRPV1 signalling complexes. Here, we hypothesize that the novel adaptor protein ankyrin-rich membrane spanning protein/kinase D interacting substrate (ARMS) interacts with TRPV1 and modulates its function in rodent DRG neurons.

Methods: We used immunohistochemistry, electrophysiology, microfluorimetry and immunoprecipitation experiments to investigate TRPV1 and ARMS interactions in DRG neurons and transfected cells.

Results: We found that TRPV1 and ARMS are co-expressed in a subpopulation of DRG neurons. ARMS sensitizes TRPV1 towards capsaicin in transfected HEK 293 cells and in mouse DRG neurons in a PKA-dependent manner. Using a combination of functional imaging and immunocytochemistry, we show that the magnitude of the capsaicin response in DRG neurons depends not only on TRPV1 expression, but on the co-expression of ARMS alongside TRPV1.

Conclusion: These data indicate that ARMS is an important component of the signalling complex regulating the sensitivity of TRPV1.

Significance: The study identifies ARMS as an important component of the signalling complex regulating the sensitivity of excitatory ion channels (TRPV1) in peripheral sensory neurons (DRG neurons) and transfected cells.

MeSH terms

  • Animals
  • Capsaicin / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • HEK293 Cells
  • Humans
  • Membrane Proteins / metabolism*
  • Mice
  • Nociceptors / drug effects
  • Nociceptors / metabolism*
  • TRPV Cation Channels / metabolism*

Substances

  • Kidins220 protein, mouse
  • Membrane Proteins
  • TRPV Cation Channels
  • TRPV1 receptor
  • Cyclic AMP-Dependent Protein Kinases
  • Capsaicin