Ads for mouthwash and chewing gum tout the fact that mint feels cool. Now researchers have found a receptor that enables us to enjoy that minty coolness. The same molecule also plays a role in sensing real cold.
Until now, researchers knew very little about how nerve cells sense cold. They did know, however, that some nerve cells that respond to cold also respond to menthol. To search for genes underlying cold and menthol detection, David Julius and colleagues at the University of California, San Francisco (UCSF), isolated cold-sensitive cells from the faces of rats. They then inserted various genes expressed by those cells into cultured cells that don't normally respond to cold or menthol. One of the genes made the cells sensitive to low temperatures as well as the minty chemical, the researchers report in the 10 February early online issue of Nature. The gene encodes a receptor, which they named CMR1 (for cold and menthol receptor). Another team, led by Ardem Patapoutian of the Scripps Research Institute in La Jolla, California, and Stuart Bevan of the Novartis Institute for Medical Sciences in London, independently identified the same gene using a different approach. They report their findings in the 11 February early online edition of Cell.
Although neither group yet knows exactly how the receptor responds to cold, the "most straightforward" explanation, Patapoutian says, is that cold temperatures alter the structure of the receptor molecule, which sits in the cell membrane. This change might allow positive sodium ions to flow into the nerve cell, increasing the likelihood it will fire an impulse. A similar adjustment could occur when menthol binds to a site on the outside of the receptor, accounting for the sensation of minty coolness.
But the newly discovered receptor is probably just the tip of the iceberg when it comes to detecting cold. "My gut feeling is that anyone who tries to explain cold transduction based on a single mechanism or molecule is going to be wrong," says Félix Viana of Miguel Hernández University in San Juan de Alicante, Spain. Indeed, Viana's research team reports the discovery of a second cold-sensitive molecule in the 11 February Advance Online Publication of Nature Neuroscience. Neurophysiologist Gordon Reid of the University of Bucharest, Romania, says that studying both molecules' activity in animals, rather than in cultured cells, will help sort out their roles.