Abstract
C. elegans PVD neurons are conserved for morphology, function and molecular determinants with mammalian polymodal nociceptors. Functions of polymodal nociceptors require activities of multiple ion channels and receptors including members of the TRP family. GTL-1, a member of the TRPM subclass of TRP channels, was previously shown to amplify PVD-mediated responses to optogenetic stimuli. Here we characterize effects of GTL-1 on PVD-mediated behavioral responses to noxious stimuli. We show that GTL-1 is required within PVD for the immediate and enduring response to thermal (cold) stimuli. But, find no significant reduction in percent animals responding to single or to repeated noxious mechanical stimuli. Nevertheless, PVD specific knockdown of gtl-1expression reduces the magnitude of responses to noxious mechanical stimuli. To understand GTL-1’s mechanism of action we expressed it in HEK293 cells. Our results show GTL-1-dependent currents induced by activation of a Gαq-coupled Designer Receptor Exclusively Activated by Designer Drugs (DREADD). In addition, using excised patches we show that GTL-1 can be activated by internal calcium. Our results are consistent with indirect, calcium dependent, activation of GTL-1 by noxious stimuli. This mechanism explains the GTL-1-dependent amplification of responses to multiple stimuli optogenetic and sensory in PVD.
Highlights
Responding appropriately to noxious, potentially injurious or injurious signals is essential for survival
Several of these channel subunits were examined for their effects on the behavioral response to optogenetic activation of PVD (Husson et al, 2012); this study identified GTL-1 as an ion channel needed within PVD for amplification of the behavioral
Previous analysis showed that PVD neurons respond to temperature downshift via the TRP channel, TRPA-1, as demonstrated by findings showing that trpa-1(lf) animals have an impaired response to rapid cooling
Summary
Responding appropriately to noxious, potentially injurious or injurious signals is essential for survival This response requires polymodal nociceptors, multi dendritic sensory neurons innervating the skin or internal organs and responding to high threshold thermal and mechanical stimuli and to noxious chemicals (Woolf and Ma, 2007; Smith and Lewin, 2009). C. elegans PVD neurons are multi dendritic neurons, conserved for structure, function, and molecular determinants with mammalian polymodal nociceptors (Chatzigeorgiou et al, 2010; Albeg et al, 2011) These neurons respond to high threshold mechanical stimuli and to cold temperatures, responses mediated, respectively, by the DEG/ENaC channel subunits, MEC-10 and DEGT-1, and the TRPA channel, TRPA-1 (Chatzigeorgiou et al, 2010). Several of these channel subunits were examined for their effects on the behavioral response to optogenetic activation of PVD (Husson et al, 2012); this study identified GTL-1 as an ion channel needed within PVD for amplification of the behavioral
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