TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour.
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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.
SubjectAmino Acid Sequence
Amino Acid Substitution
Caenorhabditis elegans Proteins
Molecular Sequence Data
Nerve Tissue Proteins
Recombinant Fusion Proteins
Structural Homology, Protein
TRPV Cation Channels
Published Version (Please cite this version)10.1038/ncomms5734
Publication InfoAnishkin, A; Chintapalli, SV; Kanju, Patrick; Liedtke, Wolfgang Bernhard; Lindy, AS; Parekh, Puja K; ... Zhu, R (2014). TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour. Nat Commun, 5. pp. 4734. 10.1038/ncomms5734. Retrieved from https://hdl.handle.net/10161/11664.
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Professor of Neurology
Research Interests in the Liedtke-Lab: Pain/ nociception Sensory transduction and -transmission TRP ion channels Water and salt equilibrium regulated by the central nervous system Visit the lab's website, download papers and read Dr. Liedtke's CV here.