The Role of the Capsaicin Receptor TRPV1 and Acid-Sensing Ion Channels (ASICS) in Proton Sensitivity of Subpopulations of Primary Nociceptive Neurons in Rats and Mice

Neuroscience. 2006 May 12;139(2):699-709. doi: 10.1016/j.neuroscience.2005.12.020. Epub 2006 Mar 3.

Abstract

A local elevation of H+-ion concentrations often occurs in inflammation and usually evokes pain by excitation of primary nociceptive neurons. Expression patterns and functional properties of the capsaicin receptor and acid-sensing ion channels suggest that they may be the main molecular substrates underlying this proton sensitivity. Here, we asked how the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) contribute to the proton response in subpopulations of nociceptive neurons from adult rats and mice (wildtype C57/Bl6, Balb/C and TRPV1-null). In cultured dorsal root ganglion neurons, whole cell patch clamp recordings showed that the majority of capsaicin-sensitive rat dorsal root ganglion neurons displayed large proton-evoked inward currents with transient ASIC-like properties. In contrast, the prevalence of ASIC-like currents was smaller in both mouse wildtype strains and more frequent in capsaicin-insensitive neurons. Transient ASIC-like currents were more frequent in both species among isolectin B4-negative neurons. A significantly reduced proton response was observed for dissociated dorsal root ganglion neurons in TRPV1 deficient mice. Unmyelinated, but not thin myelinated nociceptors recorded extracellularly from TRPV1-null mutants showed a profound reduction of proton sensitivity. Together these findings indicate that there are significant differences between rat and mouse in the contribution of TRPV1 and ASIC subunits to proton sensitivity of sensory neurons. In both species ASIC subunits are more prevalent in the isolectin B4-negative neurons, some of which may represent thin myelinated nociceptors. However, the main acid-sensor in isolectin B4-positive and isolectin B4-negative unmyelinated nociceptors in mice is TRPV1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels
  • Amiloride / pharmacology
  • Animals
  • Cells, Cultured
  • Chi-Square Distribution
  • Electric Stimulation / methods
  • Female
  • Ganglia, Spinal / cytology
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Lectins / metabolism
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology
  • Nerve Fibers / radiation effects
  • Nerve Tissue Proteins / physiology*
  • Neurons, Afferent / classification
  • Neurons, Afferent / physiology*
  • Nociceptors / physiology*
  • Patch-Clamp Techniques / methods
  • Rats
  • Skin / innervation
  • Sodium Channel Blockers / pharmacology
  • Sodium Channels / physiology*
  • TRPV Cation Channels / deficiency
  • TRPV Cation Channels / physiology*

Substances

  • Acid Sensing Ion Channels
  • Lectins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Sodium Channel Blockers
  • Sodium Channels
  • TRPV Cation Channels
  • Amiloride