Finally, TRPC1-deficient mice have

reduced firing rates in Aβ-fibers and reduced probability of withdrawal from light touch ( Garrison et al., 2012). A reduction of TRPC1 has a more dramatic effect on the ability of the animals to respond to the inflammation mediators, LBH589 in vivo prostaglandin E2 and serotonin ( Alessandri-Haber et al., 2009). Thus, loss of TRP channels has subtle effects on baseline responses and significant effects on the ability of animals to respond to inflammation. Over the past decades, a great deal of attention has focused on discovering the protein partners that form MeT channels in somatic mechanoreceptors. Two classes of ion channel proteins are leading candidates: DEG/ENaC and TRP channel proteins. Two others have recently joined their ranks: Piezo and TMC. Here, we surveyed the literature to establish that most, if not all mechanoreceptor neurons in worms, flies, and mice express multiple DEG/ENaC and TRP channel proteins. Piezo is expressed in a subset of somatosensory neurons

PR-171 price in mice, but its representation relative to other channels is not known. Little is known about expression of TMC proteins in mechanoreceptor neurons. But, the landscape of ion channel coexpression in mechanoreceptor neurons is only beginning to be mapped. Future work aimed at refining such maps for mammalian mechanoreceptor neurons will be critical for deeper understanding. Also, each of these potential MeT channel subunits operates within a large company of other ion channel actors that increase the complexity, flexibility, and robustness of somatosensory neuron function. Both DEG/ENaC and TRP channel proteins can function as essential, pore-forming subunits of MeT channels in three classes of mechanoreceptor neurons in worms: the touch receptor neurons, the CEP texture sensors, and the ASH nociceptors. Unexpectedly, some mechanoreceptor neurons rely on a single class of channels to detect mechanical cues (TRNs and CEP), while others (ASH) use at least two, genetically and biophysically distinct channels. Although such

functional redundancy has been established only in invertebrates so far, it could those explain some of the notable failures of genetic deletion of putative MeT channel subunits to disrupt touch and pain sensation in mice. From worms we also learn that some, but not all pore-forming MeT channel subunits are essential for mechanosensation. This situation is likely to exist in other mechanoreceptor neurons, including those responsible for touch and pain sensation in mammals. These findings recommend adopting a cautionary stance in interpreting the modest effects of genetic deletion of a single putative MeT channel subunit. Somatic sensation of gentle and noxious mechanical cues gives rise to our sense of touch and acute pain and also provides crucial information that regulates body movements and essential functions like blood pressure.