MechanoTRPs and TRPA1

Genetic and molecular searches in animals identify two families of ion channels used by specialized mechanosensory cells. These are the degenerin/epithelial Na+ channels (Deg/ENaCs) and transient receptor potential (TRP) channels. Some of these channels open in response to mechanical forces and/or mediate cellular responses to mechanical stimulation. TRPA1 is expressed in nociceptive neurons of peripheral ganglia and in the sensory epithelia of the inner ear. In nociceptors, TRPA1 forms chemosensitive channels that mediate the response to exogenous pain-producing chemicals as well as to the endogenous proalgesic bradykinin (BK). More indirect evidence suggests that TRPA1 might also form mechanosensory channels. Some of the TRP channels that mediate mechanical responses are not necessarily mechanically gated. For example, TRPV4 mutant mice have reduced sensitivity to noxious tactile stimulation, and heterologously expressed TRPV4 opens in response to hypotonic solution (which induces cell swelling and thus stretches membranes). TRPA1 genes in mammals are large, occupy around 50kb of chromosomal DNA and are encoded by at least 27 exons. In humans, the TRPA1 gene is located on chromosome 8q13.