ABSTRACT
Introduction............................................................................................................177 Cold Sensing and Menthol ....................................................................................178 The Hunt for a Menthol Receptor.........................................................................178 The Cloning of a Cold and Menthol Receptor .....................................................180 TRPM8 Has Properties Similar to Those of Cold Receptors ..............................180 Other Cooling Compounds Activate TRPM8 .......................................................182 Regulation of TRPM8 Currents ............................................................................183 Mechanism of Cold Activation..............................................................................184 A Role for TRPM8 Outside the Nervous System ................................................185 Conclusions............................................................................................................186 References..............................................................................................................186
Our sensory systems are able to detect subtle changes in ambient temperature, due to the coordinated efforts of thermosensory neurons. At the level of the primary afferent nerve, the site at which thermal stimuli are converted into neuronal activity, temperature-sensitive members of the TRP channel family are found. Remarkably, the range of temperatures that these channels respond to covers the entire perceived temperature spectrum, from warm to painfully hot, from pleasingly cool to excruciatingly cold [1]. Moreover, many of these channels are receptors for ligands that elicit distinct psychophysical sensations, such as the heat associated with capsaicin and the cold felt with menthol. The latter of these was influential in the discovery of the first TRP channel shown to be responsive to temperatures in the cold range (
