Nociceptive Ion Channels: mechanisms of activation

Scripps Research Institute, The, La Jolla CA

Investigators

Linked publications & trials

Abstract

While we usually take sensations such as pain, warmth or cold for granted, the molecules involved in these processes orchestrate a complex biological response to the outside world and remain almost a complete mystery. The sense of touch consists of the perception of multiple discrete types of thermal, mechanical and chemical stimuli. A great deal remains unknown about the genes involved in sensing these stimuli. With the completion of the human genome project, we have powerful new methods to identify these elusive sensory molecules. Using such tools, we recently cloned a novel sensory receptor, TRPA1, which responds to both painful cold stimuli and compounds known elicit painful sensations in humans. TRPA1 is a member of the Transient Receptor Potential (TRP) ion channel family;six members of this family respond to various temperatures. TRPA1 is highly conserved among mammals, flies, and worm. In mice, TRPA1 is expressed in sensory neurons thought to respond to several painful modalities such as heat, cold and mechanical injury. Upon activation of TRPA1 in sensory neurons, positively charged ions enter the neuron, which then fires and sends a pain signal to the brain. We wish to understand more about the consequences of TRPA1 activation in pain biology and sensation. TRPA1 is multi-modal in its activation. What other painful stimuli activate TRPA1? Mechanistically, how can a single receptor respond to so many stimuli? Can we learn more about nociceptive signaling and TRP channel signaling pathways by studying the role of TRPA1 in C. elegans?