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

• Published in: Nature communications Vol. 5; no. 1; p. 4734
• Main Authors: Lindy, Amanda S., Parekh, Puja K., Zhu, Richard, Kanju, Patrick, Chintapalli, Sree V., Tsvilovskyy, Volodymyr, Patterson, Randen L., Anishkin, Andriy, van Rossum, Damian B., Liedtke, Wolfgang B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.09.2014; Nature Publishing Group; Nature Pub. Group
• Subjects: 59/5; 631/378/2620/410; 631/45/269/1153; 64; 64/11; 96; 96/35; Amino Acid Sequence; Amino Acid Substitution; Amino acids; Animals; Avoidance Learning - physiology; Biochemistry; Biology; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Calcium - metabolism; Calcium Signaling; Gene Expression; Humanities and Social Sciences; Ion Transport; Models, Molecular; Molecular Sequence Data; multidisciplinary; Mutation; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurobiology; Neurosciences; Nociception - physiology; Nociceptors - cytology; Nociceptors - metabolism; Pain; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Science; Science (multidisciplinary); Sequence Alignment; Signal transduction; Structural Homology, Protein; TRPV Cation Channels - chemistry; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; North Carolina; California; United States > US; Pennsylvania
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms5734

Animals need to sense and react to potentially dangerous environments. TRP ion channels participate in nociception, presumably via Ca 2+ 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 Ca 2+ influx. Within the selectivity filter, M 601 -F 609 , Y604G strongly reduces avoidance behaviour and eliminates Ca 2+ transients. Y604F also abolishes Ca 2+ transients in ASH, while sustaining avoidance behaviour, yet it disrupts behavioral plasticity. Homology modelling of the OSM-9 pore suggests that Y 604 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. TRPs are calcium-permeable channels involved in the sensing of damaging stimuli but the relationship between calcium influx and pain behaviour has been elusive. Here the authors find that the TRP channel OSM-9 functions as an ion channel in vivo in C. elegans , and establish residues that are critical for worm pain-like behaviour.