Sensory discrimination between innocuous and noxious cold by TRPM8-expressing DRG neurons of rats

Mol Pain. 2012 Oct 24;8:79. doi: 10.1186/1744-8069-8-79.

Abstract

The TRPM8 channel is a principal cold transducer that is expressed on some primary afferents of the somatic and cranial sensory systems. However, it is uncertain whether TRPM8-expressing afferent neurons have the ability to convey innocuous and noxious cold stimuli with sensory discrimination between the two sub-modalities. Using rat dorsal root ganglion (DRG) neurons and the patch-clamp recording technique, we characterized membrane and action potential properties of TRPM8-expressing DRG neurons at 24°C and 10°C. TRPM8-expressing neurons could be classified into TTX-sensitive (TTXs/TRPM8) and TTX-resistant (TTXr/TRPM8) subtypes based on the sensitivity to tetrodotoxin (TTX) block of their action potentials. These two subtypes of cold-sensing cells displayed different membrane and action potential properties. Voltage-activated inward Na(+) currents were highly susceptible to cooling temperature and abolished by ~95% at 10°C in TTXs/TRPM8 DRG neurons, but remained substantially large at 10°C in TTXr/TRPM8 cells. In both TTXs/TRPM8 and TTXr/TRPM8 cells, voltage-activated outward K(+) currents were substantially inhibited at 10°C, and the cooling-sensitive outward currents resembled A-type K(+) currents. TTXs/TRPM8 neurons and TTXr/TRPM8 neurons were shown to fire action potentials at innocuous and noxious cold temperatures respectively, demonstrating sensory discrimination between innocuous and noxious cold by the two subpopulations of cold-sensing DRG neurons. The effects of cooling temperatures on voltage-gated Na(+) channels and A-type K(+) currents are likely to be contributing factors to sensory discrimination of cold by TTXs/TRPM8 and TTXr/TRPM8 afferent neurons.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Cold Temperature*
  • Female
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Ganglia, Spinal / pathology*
  • Ganglia, Spinal / physiopathology
  • Ion Channel Gating / drug effects
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism*
  • Sensory Receptor Cells / pathology*
  • TRPM Cation Channels / metabolism*
  • Tetrodotoxin / toxicity

Substances

  • TRPM Cation Channels
  • Trpm8 protein, rat
  • Tetrodotoxin