title: 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 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.
authors.affiliation: 1] Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Neurology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Lindy
authors.affiliation: Department of Neurology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Puja K
authors.initials: PK
authors.lastname: Parekh
authors.affiliation: Department of Neurology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kanju
authors.affiliation: 1] Department of Membrane Biology and Physiology, University of California, Davis, California 95616, USA [2] Department of Biochemistry and Molecular Medicine, University of California, Davis, California 95616, USA.
authors.forename: Sree V
authors.initials: SV
authors.lastname: Chintapalli
authors.affiliation: Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Tsvilovskyy
authors.affiliation: 1] Department of Membrane Biology and Physiology, University of California, Davis, California 95616, USA [2] Department of Biochemistry and Molecular Medicine, University of California, Davis, California 95616, USA.
authors.forename: Randen L
authors.initials: RL
authors.lastname: Patterson
authors.affiliation: 1] Center for Computational Proteomics, The Pennsylvania State University, University Park, Pennsylvania 16801, USA [2] Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16801, USA.
authors.forename: Andriy
authors.initials: A
authors.lastname: Anishkin
authors.affiliation: 1] Center for Computational Proteomics, The Pennsylvania State University, University Park, Pennsylvania 16801, USA [2] Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16801, USA.
authors.forename: Damian B
authors.initials: DB
authors.lastname: van Rossum
authors.affiliation: 1] Department of Neurology, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Duke University Clinics for Pain and Palliative Care, 932 Morreene Road, Durham, North Carolina 27705, USA [3] Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA [4] Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Wolfgang B
authors.initials: WB
authors.lastname: Liedtke
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D015870:Gene Expression; D017136:Ion Transport; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D059225:Nociception / Q000502:physiology*; D009619:Nociceptors / Q000166:cytology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; C108820:OSM-9 protein, C elegans; D011993:Recombinant Fusion Proteins; D050916:TRPV Cation Channels; D002118:Calcium