TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour

Abstract

Animals need to sense and react to potentially dangerous environments. TRP ion channels participate in nociception, presumably via Ca2+ influx, in most animal species. However, the relationship between ion permeation and animals’ nocifensive behaviour is unknown. Here we use an invertebrate animal model with relevance for mammalian pain. We analyse the putative selectivity filter of OSM-9, a TRPV channel, in osmotic avoidance behaviour of Caenorhabditis elegans. Using mutagenized OSM-9 expressed in the head nociceptor neuron, ASH, we study nocifensive behaviour and Ca2+ influx. Within the selectivity filter, M601-F609, Y604G strongly reduces avoidance behaviour and eliminates Ca2+ transients. Y604F also abolishes Ca2+ transients in ASH, while sustaining avoidance behaviour, yet it disrupts behavioral plasticity. Homology modelling of the OSM-9 pore suggests that Y604 may assume a scaffolding role. Thus, aromatic residues in the OSM-9 selectivity filter are critical for pain behaviour and ion permeation. These findings have relevance for understanding evolutionary roots of mammalian nociception.

Interaction between the Linker, Pre-S1, and TRP Domains Determines Folding, Assembly, and Trafficking of TRPV Channels

“…Similar to previous dynamics studies (Lindy et al, 2014;Poblete et al, 2015;Teng et al, 2015), we used the structural data available for rTRPV1 to simulate 100 ns of both rTRPV1 and hTRPV4 (Movies S1 and S2). First, rTRPV1 presented a mean of 4.3 ± 2.1 hydrogen bonds within 3 Å from K425 and hTRPV4 presented 5.6 ± 1.9 bonds within 3 Å from K462 ( Figure S7).…”

Dopamine receptor DOP-4 modulates habituation to repetitive photoactivation of a C. elegans polymodal nociceptor

“…Photoactivation with ChR2 bypassed sensory transduction, suggesting that at least one locus of plasticity lies downstream from cell excitation. Earlier work using naturally sensed cues implicated the G-protein g-subunit GPC-1, the TRPV-like channel OSM-9, and dopamine signaling in behavioral decrement associated with repeated or prolonged ASH activation (Hilliard et al 2005;Ezcurra et al 2011;Lindy et al 2014). In our optogeneticbased assay, dopamine deficient animals showed altered habituation; however loss of GPC-1 or OSM-9 had no effect on the ASH-mediated response or plasticity (Fig.…”

“…In previous research, the G-protein g-subunit GPC-1, the TRPVlike channel OSM-9, and dopamine signaling have all been implicated in the behavioral decrement associated with repeated or prolonged exposure to stimuli naturally detected by ASH (Hilliard et al 2005;Ezcurra et al 2011;Lindy et al 2014). We investigated whether mutations in genes encoding GPC-1, OSM-9, or CAT-2 (tyrosine hydroxylase, the rate limiting enzyme in dopamine biosynthesis) would similarly alter the decrement in response to repeated ASH photoactivation.…”

“…ASH neurons are especially interesting in the context of habituation because of the diversity and salience of the cues they detect: toxic volatile and nonvolatile repellents, as well as osmotic pressure and physical contact (Bargmann et al 1990; Kaplan and Horvitz 1993;Hilliard et al 2002Hilliard et al , 2005. Although an organism might not be expected to habituate to potentially lethal stimuli, repeated or prolonged exposure to naturally occurring ASHsensed stimuli leads to a decreased likelihood of responding that is mostly stimulus specific (Hart et al 1999;Ezcurra et al 2011;Hilliard et al 2005;Lindy et al 2014). Monitoring calcium transients in ASH, Hilliard et al (2005) showed that the behavioral decrement correlates with a decrease in ASH cellular responsiveness and that both are at least partially dependent on GPC-1, a G-protein g-subunit.…”

“…Monitoring calcium transients in ASH, Hilliard et al (2005) showed that the behavioral decrement correlates with a decrease in ASH cellular responsiveness and that both are at least partially dependent on GPC-1, a G-protein g-subunit. More recently, Lindy et al (2014) found that reduced responding associated with prolonged exposure to hypertonicity depends on calcium flux through the TRPV-like channel OSM-9. As with tap habituation (Kindt et al 2007), the decrement to ASH-sensed stimuli is affected by feeding status, with the presence of food promoting responding to repeated or prolonged exposure to the water-soluble repellent CuCl 2 (Ezcurra et al 2011).…”