Two different avian cold-sensitive sensory neurons: Transient receptor potential melastatin 8 (TRPM8)-dependent and -independent activation mechanisms

Neuropharmacology. 2016 Dec:111:130-141. doi: 10.1016/j.neuropharm.2016.08.039. Epub 2016 Aug 31.


Sensing the ambient temperature is an important function for survival in animals. Some TRP channels play important roles as detectors of temperature and irritating chemicals. There are functional differences of TRP channels among species. TRPM8 in mammals is activated by cooling compounds and cold temperature, but less information is available on the functional role of TRPM8 in avian species. Here we investigated the pharmacological properties and thermal sensitivities of chicken TRPM8 (cTRPM8) and cold-sensitive mechanisms in avian sensory neurons. In heterologously expressed cTRPM8, menthol and its derivative, WS-12 elicited [Ca2+]i increases, but icilin did not. In chicken sensory neurons, icilin increased [Ca2+]i, in a TRPA1-dependent manner. Icilin selectively stimulated heterologously expressed chicken TRPA1 (cTRPA1). Similar to mammalian orthologue, cTRPM8 was activated by cold. Both heterologous and endogenous expressed cTRPM8 were sensitive to mammalian TRPM8 antagonists. There are two types of cold-sensitive cells regarding menthol sensitivity in chicken sensory neurons. The temperature threshold of menthol-insensitive neurons was significantly lower than that of menthol-sensitive ones. The population of menthol-insensitive neurons was large in chicken but almost little in mammals. The cold-induced [Ca2+]i increases were not abolished by the external Ca2+ removal or by blockades of PLC-IP3 pathways and ryanodine channels. The cold stimulation failed to evoke [Ca2+]i increases after intracellular Ca2+ store-depletion. These results indicate that cTRPM8 acts as a cold-sensor similar to mammals. It is noteworthy that TRPM8-independent cold-sensitive neurons are abundant in chicken sensory neurons. Our results suggest that most of the cold-induced [Ca2+]i increases are mediated via Ca2+ release from intracellular stores and that these mechanisms may be specific to avian species.

Keywords: Ca(2+) mobilization; Intracellular Ca(2+) stores; Menthol; Sensory neuron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / pharmacology
  • Animals
  • Avian Proteins / physiology*
  • Calcium Signaling / drug effects
  • Chickens
  • Cold Temperature
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / physiology
  • HEK293 Cells
  • Humans
  • Menthol / analogs & derivatives
  • Menthol / pharmacology
  • Pyrimidinones / pharmacology
  • TRPM Cation Channels / antagonists & inhibitors
  • TRPM Cation Channels / metabolism
  • TRPM Cation Channels / physiology*
  • Thermoreceptors / drug effects
  • Thermoreceptors / physiology*
  • Thermosensing / drug effects
  • Thermosensing / physiology*
  • Transient Receptor Potential Channels / antagonists & inhibitors
  • Transient Receptor Potential Channels / metabolism
  • Transient Receptor Potential Channels / physiology


  • Anilides
  • Avian Proteins
  • N-(4-methoxyphenyl)-4-menthone-3-carboxamide
  • Pyrimidinones
  • TRPM Cation Channels
  • Transient Receptor Potential Channels
  • Menthol
  • icilin