1. TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour.
- Author
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Lindy AS, Parekh PK, Zhu R, Kanju P, Chintapalli SV, Tsvilovskyy V, Patterson RL, Anishkin A, van Rossum DB, and Liedtke WB
- Subjects
- Amino Acid Sequence, Amino Acid Substitution, Animals, Caenorhabditis elegans Proteins genetics, Caenorhabditis elegans Proteins metabolism, Calcium Signaling, Gene Expression, Ion Transport, Models, Molecular, Molecular Sequence Data, Mutation, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Nociceptors cytology, Recombinant Fusion Proteins chemistry, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Sequence Alignment, Structural Homology, Protein, TRPV Cation Channels genetics, TRPV Cation Channels metabolism, Avoidance Learning physiology, Caenorhabditis elegans physiology, Caenorhabditis elegans Proteins chemistry, Calcium metabolism, Nerve Tissue Proteins chemistry, Nociception physiology, Nociceptors metabolism, TRPV Cation Channels chemistry
- Abstract
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.
- Published
- 2014
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