Transient receptor potential (TRP) channels were first described in Drosophila, where photoreceptors carrying trp gene mutations exhibited a transient voltage response to continuous light. Since that time the TRP channel family has grown to include at least 20 members. TRP channels exhibit a wide variety of functions: invertebrate phototransduction; responses to painful stimuli and to moderate temperature changes; regulation of intracellular calcium stores; receptorúmediated excitation; and modulation of the cell cycle. Despite the clear physiological importance of TRP channels, little is known about what regulates their function or about their structure. One type of TRP channel, TRPV1, is a polymodal receptor that integrates a number of painful stimuli. These stimuli include: noxious heat, with a threshold of approximately 42úC; extracellular acidification, with a pKa of about 5.3; anandamide and other arachidonic acid metabolites; and capsaicin, a pungent extract from plants in the Capsicum family. My lab studies the molecular mechanisms of activation and regulation of TRPV1 and TRPM8 channels which function not only as intrinsic sensors of the cellular environment but also in the whole organism. We use a combination of electrophysiological, molecular biology and biochemical techniques to study their structural and functional properties.