RESEARCH SUMMARY

The first TRP channel was identified in 1977 as a phototransduction mutant in Drosophila (Minke, 1977). Since that time the TRP channel family has grown to include at least 20 members (Clapham et al., 2001). The importance of TRP channels is demonstrated by the wide variety of their proposed functions: invertebrate phototransduction; responding to painful stimuli; responding to moderate temperature changes; repletion of intracellular calcium stores; receptor–mediated excitation; and modulation of the cell cycle (reviewed in (Clapham et al., 2001; Montell, 2001; Montell et al., 2002). Despite the clear physiological importance of TRP channels, little is known about what regulates their function. 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 42C; extracellular acidification, with a pKa of about 5.3 (Caterina et al., 1997; Jordt et al., 2000); anandamide and other arachidonic acid metabolites (Smart et al., 2000); and capsaicin, a pungent extract from plants in the Capsicum family (Szallasi and Blumberg, 1999; Caterina and Julius, 2001).

My lab studies the molecular mechanisms of activation and regulation of TRPV1 channels. We use electrophysiology to study their functional properties, molecular biology to control their primary sequence (i.e. make mutations), and biochemistry to examine their interactions with other proteins. We are particularly interested in interactions. For ion channels, we must consider interactions between subunits within one channel, interactions with regulator proteins, interactions with the membrane, and interactions with small molecules such as second messengers. It is through understanding what interactions occur, when they occur, and how they have their effect that we make progress in addressing the function and role of ion channels within cells.