May 20, 2002 A group of researchers from The Scripps Research Institute (TSRI) and the Genomics Institute of the Novartis Research Foundation (GNF) have identified and cloned the first-known gene that makes skin cells able to sense warm temperatures.
In an article appearing in the journal Science, a group led by Ardem Patapoutian of TSRI and Stuart Bevan of Novartis describes the protein the gene makes, a type of transient receptor potential (TRP) channel called "TRPV3." This membrane protein opens when it senses a certain temperature and allows ions to pass through and cause an electrical potential that signals the brain.
"This protein may be an important target for drugs," says Patapoutian, "because, like other TRP channels, it may be involved in inflammation and pain-mediation."
Significantly, TRPV3 is the first temperature-sensing molecule identified that becomes activated at warm and hot temperatures, 33° C (91.5° F) and above. And it is the first temperature-sensing channel found in keratinocytes, which are the major type of cell in the skin.
Previously, scientists had known that humans and other vertebrate animals use specialized neurons located in the spinal column that are connected to the skin and organs through long axons to sense temperature, pressure, and other physical stimuli. Expressed on these axons are the same sort of TRP channels as the one in the current study, and in the last few years scientists have identified them as the "molecular thermometers" that detect hot and cold temperatures in the skin and relay that information back to the brain.
Earlier this year, the TSRI and GNF group identified and cloned the gene—called TRPM8— that codes for the first-known signaling molecule that helps the body sense cold temperatures and the cooling compound, menthol. That led them in part to the current molecule.
They knew that TRPM8 detects cold. And another set of channels in the spinal cord were known to detect noxious heat. Patapoutian and his team reasoned that one or more molecules like TRPV3 must be able to detect warm temperatures.
"We have shown for the first time that skin cells are capable of detecting heat through molecules similar to those in heat-sensing neurons," says Patapoutian.
Around 33° C, TRPV3 becomes activated, opens, and allows an influx of positively-charged ions into the cell—an electrical signal that presumably alerts the brain of the temperature.
It is not known how this signal is communicated to the brain, since keratinocytes, unlike neurons, have no direct link with the central nervous system. Keratinocytes do, however, touch nerve fibers, and it may be through these contacts that the temperatures are communicated—something that the team is trying to verify.
The channel's similarity to another temperature-sensing ion channel called VR1 suggests that TRPV3 may be a target for pain therapeutics. VR1 is involved in inflammation and in communicating pain to the brain, and several compounds that block its action are currently under investigation for chronic pain indications.
Similarly, compounds that block TRPV3's action may also be useful for fighting chronic pain.
The research article "A novel heat-sensitive TRP channel expressed in keratinocytes" is authored by Andrea M. Peier, Alison J. Reeve, David A. Andersson, Aziz Moqrich, Taryn J. Earley, Anne C. Hergarden, Gina M. Story, Sian Colley, John B. Hogenesch, Peter McIntyre, Stuart Bevan, and Ardem Patapoutian and appears in the online version of Science on May 16, 2002.
The research was funded by a grant to TSRI from Novartis.
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