The first response to mechanical stimulus was not affected, but the magnitude of the Tyrosine Kinase Inhibitor Library second response was reduced (Kindt et al., 2007). A role for the TRPV channel subunit OSM-9 is evident from the finding that osm-9 mutant OLQ neurons lack mechanically-evoked calcium transients ( Chatzigeorgiou et al., 2010). Because MRCs have yet to be measured in this mechanoreceptor neuron, it is not known whether loss of TRPA-1 or OSM-9 affect MRCs or the events that follow their activation. These examples in C. elegans nematodes establish the rule that mechanoreceptor neurons commonly express multiple

DEG/ENaC and TRP channel proteins and that these channels operate together to enable proper sensory function. The ability to directly measure

MRCs in vivo has revealed that both DEG/ENaC and TRP channels can form MeT channels. Evidence from the ASH and PVD nociceptors suggests that some TRP channels are essential for posttransduction events needed for sensory signaling. These case studies provide evidence for the idea that TRP channels can be crucial elements in both sensory transduction and in post-transduction signaling. They also illustrate the powerful insights available when detailed physiological analysis of identified mechanoreceptor neurons is merged with genetic dissection. It is rare for deletion of a single DEG/ENaC gene to induce strong behavioral defects in C. elegans. Indeed, there is only one such DEG/ENaC gene known so far: mec-4. By contrast, deleting the DEG/ENaC genes mec-10, deg-1, unc-8, and unc-105 fails to produce clear behavioral phenotypes, although gain-of-function alleles significantly disrupt several behaviors. INCB024360 clinical trial Though only a subset of the DEG/ENaC genes have been studied in this way, these findings suggest there is considerable redundancy in C. elegans mechanosensation. The case of mec-4 and mec-10 illustrate this idea clearly: both genes are coexpressed in the TRNs and encode pore-forming subunits of the MeT channel required for gentle touch sensation ( O’Hagan et al.,

2005). Whereas deleting mec-4 eliminates mechanoreceptor currents and behavioral responses to touch, deleting mec-10 produces a mild defect in touch sensation and has little effect on Rolziracetam mechanoreceptor currents ( Arnadóttir et al., 2011). The peripheral nervous system of Drosophila larvae has three main types of neurons ( Bodmer et al., 1987, Bodmer and Jan, 1987 and Ghysen et al., 1986). External sensory and chordotonal neurons have a single sensory dendrite and innervate specific mechanosensory organs. In contrast, multidendritic neurons have a variable number of fine dendritic processes that lie beneath the epidermis and do not innervate a specific structure. Different subclasses of these neurons provide information about touch and body position as well as function as nociceptors ( Hughes and Thomas, 2007, Song et al., 2007 and Zhong et al., 2010).