After just a few seconds of swishing, the familiar cold and semi-painful flavor of mouthwash sets in. It’s an odd sensation, because the liquid isn’t actually cold—it just feels like it is. But, how can we feel a temperature that’s not there? The answer comes from TRPM8—a gene that helps us stay warm, and has done so for thousands of years.
With an average temperature of 98.6oF, the human body is a walking heat factory. Most of this heat is generated when proteins in our body break down chemical bonds—a normal activity that allows our cells to harvest energy from various molecules and use it to stay healthy. Each time a chemical bond is broken, some of the energy from that bond escapes in the form of thermal radiation (better known as heat)1. With trillions of cells acting at the same time, you can see how our body begins to radiate large amounts of thermal energy.
What’s important to note here is that thermal energy has the power to help our body, but it can also hurt us. This heat can be absorbed by other molecules in our body, which then use that energy to function. Too much heat can cause the molecules in our body to be overwhelmed with energy and break apart. Too little energy, and our cells will putter out like a car without gas. To make sure our body temperature is just right, we rely on genes like TRPM8.
Spicy food and pit vipers
TRPM8 isn’t the only gene that can sense temperature changes. A similar gene known as TRPA1 is used by humans to detect foods—particularly spicy foods—or potential irritants that give us a hot sensation. In pit vipers, a change to the TRPA1 gene gives them infrared vision8. Read about it here.
TRPM8 is a gene in our DNA that helps us know when our environment is becoming, or already is, cold. This “cold gene” tells our body how to make the TRPM8 protein (proteins often have the same name as the gene that codes for them) which acts as a temperature-sensitive gatekeeper in specialized neurons2-4. Here’s how it works: Neurons are able to send electrical signals by controlling the flow of electrically charged molecules—calcium, sodium, potassium—into and out of each neuron. TRPM8 acts like a gate that can open to allow some of these molecules to flood the cell, but only under certain conditions. One of those conditions is when our body comes into contact with something cold5,6.
Neurons are woven throughout the human body, where they help coordinate muscle contraction, monitor food digestion, and keep track of environmental temperature. The TRPM8 protein can be found in temperature- and pain-sensing neurons in the skin6. There, the TRPM8 protein helps by triggering an electrical pulse when our body comes into contact with cold temperatures. As a result, our body may begin shivering, contracting blood vessels, or taking other steps to prevent our body temperature from changing6.
Aside from cold temperatures, some natural molecules can also cause the TRPM8 protein to open up and trigger an electrical pulse. Menthol—commonly found in mint plants or in minty products like mouthwashes, mint gums, and vaporubs—is one such molecule. The menthol in mouthwash triggers the TRPM8 protein and causes you to sense that the liquid is cold, even though it is not2,4,6.
Is Chewbacca cool?
Humans used to be covered in a dense mat of hair, similar to Chewbacca from Star Wars. As we evolved, we had to lose some of that hair to help with our temperature regulation. Find out more in this fun article about ancient humans and Chewbacca.
Curiously, recent research suggests that changes in the DNA that affect how much of the TRPM8 protein is made may have helped humans adapt to northern climates3. Approximately 100,000 years ago, anatomically modern humans left Africa and began to spread across the Eurasian continent7. Having evolved in the hot African climate, the cold northern territories of Eurasia likely proved to be a difficult place for them to survive. However, they developed changes in their DNA over time that helped them adapt to colder weather. A recent study looking at TRPM8 found that people with ancestry from these colder, northern climates like Finland often have a variant in the DNA that alters how much TRPM8 protein is made. This is in contrast to people in Nigeria who rarely have this variant3. Further analysis suggested that the variant first appeared in Africa, but didn’t become common until people journeyed north3. Exactly why this change in TRPM8 was advantageous isn’t clear, but it provides some interesting questions for future research.
The ability to maintain our body heat with such consistency is nothing short of amazing. It’s a constant battle between generating and releasing thermal energy so as to not get too hot, while also retaining just the right amount of heat. It’s an elaborate network that, in some cases, starts with TRPM8 and reminds us that genetics can be pretty… cool.
- Bene, Victor E. Del. “Temperature.” Advances in Pediatrics., U.S. National Library of Medicine, 1 Jan. 1990, www.ncbi.nlm.nih.gov/books/NBK331/.
- McKemy, David D. “TRPM8: The Cold and Menthol Receptor.” Advances in Pediatrics., U.S. National Library of Medicine, 1 Jan. 1970, www.ncbi.nlm.nih.gov/books/NBK5238/.
- Key, Felix M. et al. “Human Local Adaptation of the TRPM8 Cold Receptor along a Latitudinal Cline.” Ed. Takashi Gojobori. PLoS Genetics 14.5 (2018): e1007298. PMC. Web. 5 Sept. 2018.
- Rath, Parthasarathi et al. “Implications of Human TRPM8 Channel Gating from Menthol Binding Studies of the Sensing Domain.” Biochemistry 55.1 (2016): 114–124. PMC. Web. 5 Sept. 2018.
- Venkatachalam, Kartik, and Craig Montell. “TRP Channels.” Annual review of biochemistry 76 (2007): 387–417. PMC. Web. 5 Sept. 2018.
- Wang, Hong, and Jan Siemens. “TRP Ion Channels in Thermosensation, Thermoregulation and Metabolism.” Temperature: Multidisciplinary Biomedical Journal 2.2 (2015): 178–187. PMC. Web. 4 Sept. 2018.