, 1995). An example of the converse situation in which fibers with distinct electrophysical properties innervate a common peripheral end organ has recently come to light: Li et al. (2011a) show that Aβ, Aδ, and C fibers all form lanceolate endings that surround hair follicles. This discovery relied on developing a suite of genetic markers that were exploited in two ways. First, they were used to determine the peripheral endings associated

with marked sensory subtypes. Second, they were used to link electrophysiological properties derived from in vivo intracellular recordings to the marker suite and hence to mechanoreceptor subtype. Thus, knowledge of conduction velocity and force sensitivity may not be sufficient to infer the identity of the peripheral organ check details being stimulated. Genetic deletion of single DEG/ENaC or TRP channel proteins in mice alters sensitivity to mechanical stimulation, but leaves both functions largely intact. While these studies cast doubt Pomalidomide on the idea that DEG/ENaC or TRP channel proteins are essential for mechanotransduction in mammals, they also suggest that the mammalian somatosensory system is robust to genetic deletion. Such robustness could reflect molecular redundancy within or between ion channel gene families. Additionally, robustness could be conferred by functional degeneracy among

mechanoreceptor neurons. The potential for degeneracy arises from the fact that skin dermatomes contain a mixture of peripheral Unoprostone sensory structures and are innervated by multiple classes of somatosensory neurons. For example, low-threshold, rapidly adapting Aβ fibers are thought to innervate both Pacinian and Meissner corpuscles in the skin (Brown and Iggo, 1967, Burgess et al., 1968 and Vallbo et al., 1995). In addition to having distinct morphologies, each of these endings also expresses different DEG/ENaC and TRP channel proteins (Calavia et al., 2010, García-Añoveros et al., 2001, Kwan et al., 2009, Price et al., 2001 and Suzuki et al., 2003b). In this scenario, loss of a single ion channel protein is expected to have only a minor effect on the entire class of such fibers. The acid-sensing ion channels or ASICs

are a vertebrate sub-division of the conserved DEG/ENaC superfamily. Most if not all of the ASIC proteins are expressed in cell bodies in the trigeminal and dorsal root ganglia (reviewed in Deval et al., 2010) and localize to the peripheral endings in the skin (Figure 2C). For instance, ASIC1 is expressed in nerves innervating Pacinian corpuscles in human skin (Calavia et al., 2010 and Montaño et al., 2009). However, genetic deletion of ASIC1 has no effect on the threshold or firing frequency of fibers innervating mouse skin (Page et al., 2004), but alters visceral sensory function (Page et al., 2004 and Page et al., 2005). ASIC2 and ASIC3 are expressed in the majority of mechanoreceptor endings in mouse skin (Figure 2C; García-Añoveros et al., 2001, Price et al.