Abstract
The detection of ambient cold is critical for mammals, who use this information to avoid tissue damage by cold and to maintain stable body temperature. The transduction of information about the environmental cold is mediated by cold-sensitive ion channels expressed in peripheral sensory nerve endings in the skin. Most transduction mechanisms for detecting temperature changes identified to date depend on transient receptor potential (TRP) ion channels. Mild cooling is detected by the menthol-sensitive TRPM8 ion channel, but how painful cold is detected remains unclear. The TRPA1 ion channel, which is activated by cold in expression systems, seemed to provide an answer to this question, but whether TRPA1 is activated by cold in neurons and contributes to the sensation of cold pain continues to be a matter of debate. Recent advances have been made in this area of investigation with the identification of several potential cold-sensitive ion channels in thermosensory neurons, including two-pore domain potassium channels (K2P), GluK2 glutamate receptors, and CNGA3 cyclic nucleotide-gated ion channels. This mini-review gives a brief overview of the way by which ion channels contribute to cold sensation, discusses the controversy around the cold-sensitivity of TRPA1, and provides an assessment of some recently-proposed novel cold-transduction mechanisms. Evidence for another unidentified cold-transduction mechanism is also presented.
Highlights
All biological processes are affected by temperature, so to maintain optimal function in the face of external thermal challenges it is crucial for animals to detect the temperature both of their bodies and the environment, and to react appropriately
The channel was found to contribute to cold responses of dorsal root ganglia (DRG) neurons in vitro, but Transient Receptor Potential Canonical 5 (TRPC5) KO mice displayed no difference in temperature preference compared to WT mice (Zimmermann et al, 2011), suggesting that the ion channel is not involved to any significant extent in physiological cold-sensation
DRG neurons responded to a 4◦C cold stimulus in mice, showing that Transient Receptor Potential Ankyrin 1 (TRPA1) expression alone does not render neurons cold-sensitive, but the amplitude of the cold-activated Ca2+ influx in these neurons was reduced after application of the selective TRPA1 antagonist HC030031, suggesting that TRPA1 does contribute to their cold responses (Memon et al, 2017)
Summary
All biological processes are affected by temperature, so to maintain optimal function in the face of external thermal challenges it is crucial for animals to detect the temperature both of their bodies and the environment, and to react appropriately. Consistent with its range of thermal activation in vitro, TRPM8 plays an important role in the sensation of non-noxious cool temperatures in vivo.
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