Editing Thermoreceptor (section)

==Mechanism of transduction==
This area of research has recently received considerable attention with the identification and cloning of the [[Transient Receptor Potential]] (TRP) family of proteins.  The transduction of temperature in cold receptors is mediated in part by the TRPM8 channel {{cn|date=October 2024}}. This channel passes a mixed inward cationic (predominantly carried by Na<sup>+</sup> ions although the channel is also permeable to Ca<sup>2+</sup>) current of a magnitude that is inversely proportional to temperature {{cn|date=October 2024}}. The channel is sensitive over a temperature range spanning about 10-35&nbsp;°C {{cn|date=October 2024}}.  TRPM8 can also be activated by the binding of an extracellular ligand. Menthol can activate the TRPM8 channel in this way. Since the TRPM8 is expressed in neurons whose physiological role is to signal cooling, menthol applied to various bodily surfaces evokes a sensation of cooling {{cn|date=October 2024}}. The feeling of freshness associated with the activation of cold receptors by menthol, particularly those in facial areas with axons in the [[Trigeminal nerve|trigeminal (V) nerve]], accounts for its use in numerous toiletries including toothpaste, shaving lotions, facial creams and the like.

Another molecular component of cold transduction is the temperature dependence of so-called leak channels which pass an outward current carried by potassium ions. Some leak channels derive from the family of [[Two-pore-domain potassium channel|two-pore (2P) domain potassium channel]]s {{cn|date=October 2024}}.  Amongst the various members of the 2P-domain  channels, some close quite promptly at temperatures less than about 28&nbsp;°C (e.g. [[KCNK4]](TRAAK), TREK) {{cn|date=October 2024}}. Temperature also modulates the activity of the [[Na+/K+-ATPase|Na<sup>+</sup>/K<sup>+</sup>-ATPase]] {{cn|date=October 2024}}. The Na<sup>+</sup>/K<sup>+</sup>-ATPase is a [[P-type pump]] that extrudes 3Na<sup>+</sup> ions in exchange for 2K<sup>+</sup> ions for each hydrolytic cleavage of ATP. This results in a net movement of positive charge out of the cell, i.e. a [[Hyperpolarization (biology)|hyperpolarizing current]]. The magnitude of this current is proportional to the rate of pump activity.

It has been suggested that it is the constellation of various thermally sensitive proteins together in a neuron that gives rise to a cold receptor.<ref>{{cite journal |vauthors=Viana F, de la Peña E, Belmonte C |year=2002 |title=Specificity of cold thermotransduction is determined by differential ionic channel expression. |url=https://www.nature.com/articles/nn809 |journal=[[Nature Neuroscience]] |volume=5 |issue=3 |pages=254–260 |doi=10.1038/nn809 |pmid=11836533 |s2cid=21291629 |url-access=subscription}}</ref> This emergent property of the neuron is thought to comprise, the expression of the aforementioned proteins as well as various voltage-sensitive channels including the hyperpolarization-activated, [[Cyclic nucleotide–gated ion channel|cyclic nucleotide-gated (HCN) channel]] and the rapidly activating and inactivating transient potassium channel (IK<sub>A</sub>).