Michael J. Caterina
Molecular Mechanisms of Mammalian Thermosensation
Molecular mechanisms of thermosensation and nociception My lab is interested in understanding how specialized cells in the nervous system detect changes in ambient temperature. Increases or decreases in tissue temperature can cause pain, pleasure, or homeostatic changes in mammals, depending upon their direction, magnitude, and anatomical location. The molecular basis of this thermosensation, however, is very poorly understood. Using expression cloning and homology-based cloning, we recently identified two heat-gated ion channels that are expressed in distinct subsets of peripheral neurons within the pain pathway. One of these proteins, VR1, is a channel that can be activated not only by noxious heat (> 43f C), but also by protons and by capsaicin (the main pungent ingredient in EhotD peppers). The second channel, VRL-1, is activated by temperatures exceeding 52f C, but is insensitive to protons or capsaicin.
Through a multidisciplinary approach involving molecular biology, biochemistry, calcium imaging, electrophysiology and mouse genetics, we are focusing on the following goals: 1) Using mouse knockouts of VR1 and VRL-1 to clarify their roles in the pain pathway. 2) Identifying novel molecules involved in the detection of cold and warm thermal stimuli by the peripheral and central nervous systems. 3) Dissecting the mechanisms by which these molecules are activated by increases or decreases in ambient temperature.