Second, loss of deg-1 eliminates 80% of the total MRC. This is not due to a general defect caused by gene mutation, however, since loss of three other ASH-expressed ion channel genes, unc-8, osm-9, and ocr-2, has no effect on MRCs. Additionally, deg-1 mutants have no effect on voltage-activated currents in ASH. Finally, mutations that alter, but do not eliminate DEG-1 decrease MRC amplitude and modify MRC ion selectivity. This last finding is critical for two reasons. First, it demonstrates that DEG-1 is expressed

in the ASH neurons, as initially reported ( Hall et al., 1997) but recently contested ( Wang et al., 2008). Second, and most critical for the present study, this finding establishes that DEG-1 is a pore-forming subunit of click here the primary channel responsible for allowing the ASH neurons to detect aversive mechanical stimuli. Mechanoreceptor currents in ASH nociceptors share several features with those reported previously

in other mechanoreceptor neurons in C. elegans ( Kang et al., 2010 and O’Hagan et al., 2005), spiders ( Juusola et al., 1994), and certain dorsal root ganglion neurons studied in vitro ( Drew et al., 2002, Hao and Delmas, 2010, Hu and Lewin, 2006 and McCarter et al., 1999). One shared feature is the kinetics of MRCs: in all of these Alpelisib in vivo cell types, currents activate rapidly following stimulation, but decay during continued stimulation. Until now, it has been assumed that a single class of ion channels is responsible for MRCs in individual mechanoreceptor neurons since their activation and decay follow a single exponential time course. Using genetic dissection and in vivo patch-clamp recording, we discovered that mechanoreceptor currents in ASH are composed of at least two distinct currents: the major deg-1-dependent current, which accounts

for more Astemizole than 80% of the peak amplitude and the minor deg-1-independent current that carries the rest. Our work contrasts with the results from other C. elegans neurons where the loss of a single channel subunit eliminated MRCs ( Kang et al., 2010 and O’Hagan et al., 2005) and is similar to findings from Drosophila bristle receptors in which the loss of NompC reduces MRCs by 90% ( Walker et al., 2000). The major and minor currents in ASH differ in their reversal potential, suggesting that distinct classes of ion channels carry these currents. Although the molecular identity of the deg-1-independent channel is not yet known, we show that it is independent of both osm-9 and ocr-2, since osm-9ocr-2;deg-1 triple mutants have MRCs that are indistinguishable from those observed in deg-1 single mutants. Candidates include nonselective cation channels such as the other 22 members of the TRP channel family in C. elegans ( Glauser et al., 2011 and Goodman and Schwarz, 2003) and the C.