Thus, even a complete block of MRCs in ASH would produce only a partial inhibition of behavioral NVP-BKM120 responses to nose touch. We then examined whether MRCs were Na+ dependent. The reversal potential for Na+ ions in our solutions was +40 mV. Wild-type MRCs were inward across a wide range of membrane potentials (Figures 2F and 4E). In control saline, inward rectification was sufficiently strong that outward currents could not be detected, even at voltages as high as +80 mV (Figure 4E). The ionic basis of such strong

inward rectification is not known but could reflect multiple factors including high calcium permeability and voltage-dependent block of outward current. Replacing extracellular Na+ with a large, monovalent cation (n-methyl-d-glucamine) dramatically decreased inward MRCs at −60 mV ( Figures 2D and 2E), shifted the reversal potential of the peak MRC to −47 mV and increased outward currents ( Figure 2F). This last effect could reflect relief of inhibition by extracellular Na+ ions as reported for ENaC channels ( Bize and Horisberger, 2007). On average, MRCs

reversed polarity at −51 ± 5 mV (mean ± SEM, n = 4) in Na+-free saline. These effects indicate that MRCs are Na+-dependent in control saline and suggest the most of the channels that carry such currents are Na+ permeable. The ASH neurons express at least two members of the DEG/ENaC gene family: deg-1 and unc-8 ( Hall et al., 1997 and Tavernarakis et al., 1997). We investigated the effect of large deletions in deg-1 and unc-8 on the generation of MRCs in the ASH neurons. Deleting unc-8 had no effect Anti-infection Compound Library on the generation of force-activated MRCs ( Figure 3A; Table 1). By contrast, loss of deg-1 reduced MRCs by 80% and MRCs in unc-8;deg-1 double null mutants were similar to those in deg-1 Org 27569 single mutants ( Figure 3A; Table 1). None of these mutations affected

voltage-activated currents in ASH thus the effects of the mutations in deg-1 are limited to MRCs ( Figures 3B and 3C). In addition to reducing current size, loss of deg-1 shifted the reversal potential of the peak MRCs to −23 ± 5 mV (mean ± SEM; n = 3; Figure 5B). These results suggest that the ion channels responsible for the deg-1-independent currents are not primarily sodium-permeable and are unlikely to be formed by the remaining UNC-8 protein. Instead, they appear to be permeable to potassium and sodium, a property of TRPV channels. Thus, deg-1, but not unc-8, is essential for the major component of MRCs in ASH. We note that while unc-8 is not required for the generation of MRCs in ASH, it remains possible that MeT channels contain both DEG-1 and UNC-8. If this scenario is correct, then our data imply that DEG-1 forms functional channels in the absence of UNC-8, but that UNC-8 is unable to function without DEG-1. A similar situation exists in C.