, 2010). Our data demonstrate that mechanoreceptor currents in ASH are carried by two genetically separable currents, but we do not know whether force activates these two currents GDC-0199 molecular weight in a sequential or parallel fashion. In any plausible sequential model, the minor current must be upstream of the major current because it remains when deg-1 is lost and thus its activation must precede activation of the major current. But, the minor current does not activate faster than the total current. Also, if the major deg-1-dependent current were activated in response to the minor current, this event must be complete in milliseconds or less. Most second messenger systems are not that rapid. While we cannot eliminate

the sequential model, we favor the parallel model and propose that ASH expresses two sensory mechanotransduction channel complexes, one of which uses DEG-1 as a pore-forming subunit. The use of multiple mechanotransduction channels may not be unique to ASH; other mechanoreceptor neurons may express multiple classes of mechanotransduction channels ( Göpfert et al., 2006 and Walker et al., 2000). This functional redundancy could account for difficulties in identifying a single channel type responsible for mechanoreceptor currents in mammalian somatosensory neurons, including nociceptors. Most animals are endowed with a complex array of sensory neurons specialized to detect mechanical energy in the form of touch, vibration, or

body movements. Such neurons vary not only in the loads and strains they detect, but also in their sensitivity. In the present work and in a prior study (O’Hagan et al., 2005), we have shown that two kinds of C. elegans Fulvestrant mouse mechanoreceptor neurons, ASH and PLM neurons, respond to force

using channels formed by DEG/ENaC proteins. The two kinds of neurons differ in their sensitivity to mechanical loads: nearly one hundred-fold higher forces are required to activate mechanoreceptor currents in ASH nociceptors (this study) than in the PLM touch receptor neurons ( O’Hagan et al., 2005). The difference in sensitivity could reside in the MeT channels themselves. In this scenario, each DEG/ENaC subunit would harbor a force sensor that links mechanical loads to channel gating, but the sensors would vary in the forces required to activate them. Alternatively, Bcl-w the primary determinant of force sensitivity could be the cellular machinery that transmits loads from the body surface to the channel proteins embedded in the sensory neuron’s plasma membrane. These two modes for establishing the exact force dependence of MeT channels in vivo are not mutually exclusive, however. Regardless of the molecular and cellular basis for the difference in sensitivity, our work establishes that both low-threshold, gentle touch receptor neurons and high-threshold nociceptors rely on DEG/ENaC proteins to form amiloride-sensitive, sodium-permeable channels responsible for MRCs in vivo.