TY - JOUR
T1 - TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour
AU - Lindy, Amanda S.
AU - Parekh, Puja K.
AU - Zhu, Richard
AU - Kanju, Patrick
AU - Chintapalli, Sree V.
AU - Tsvilovskyy, Volodymyr
AU - Patterson, Randen L.
AU - Anishkin, Andriy
AU - Van Rossum, Damian B.
AU - Liedtke, Wolfgang B.
N1 - Funding Information:
This work was supported by grant support from the Esther A. and Joseph Klingenstein Fund (New York, NY; to W.B.L.), the Whitehall Foundation (Boca Raton, FL; to W.B.L.) and startup funds from Duke University (to W.B.L.). Further support is acknowledged from the Searle Young Investigators Award and startup money from Pennsylvania State University (PSU) (to R.L.P.), the National Science Foundation 428-15 691M (to R.L.P. and D.B.v.R.) and the National Institutes of Health R01 GM087410-01 (to R.L.P., D.B.v.R). This project was also funded by a grant from the Pennsylvania Department of Health using Tobacco Settlement Funds (to D.B.v.R.). The Pennsylvania Department of Health specifically disclaims responsibility for any interpretations or conclusions. We acknowledge inspirational discussion with Dr Roderick MacKinnon (The Rockefeller University) during an early stage of the study. We thank Dr Cornelia I. Bargmann of The Rockefeller University for her advice and for use of specialized imaging equipment, also Drs Sreekanth Chalasani and Manuel Zimmer from her laboratory for experimental guidance with in vivo calcium imaging as well as stimulating discussions. Suk Hee Lee (Duke University) provided excellent technical assistance. Drs Darren Boehning (UTMB Galveston), Marc Marti-Renom (Valencia, Spain), Seok-Yong Lee, Fan Wang, Sidney A. Simon, Hiroaki Matsunami, Joerg Grandl, Farshid Guilak, Dong Yang and David Tobin (all Duke University) provided insightful comments. We wish to thank Drs Sam Johnson and Dan Tracey (Duke University) for their help with microscopy. Special gratitude is expressed towards Dr Marc Freichel (University of Heidelberg, Germany) for his steadfast and unwavering commitment to study electrophysiological properties of the OSM-9 pore in heterologous cells as well as his insightful suggestions. Special credit goes to Dr Andriy Anishkin who conducted all computational refinement of the models.
PY - 2014/9/2
Y1 - 2014/9/2
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms5734
DO - 10.1038/ncomms5734
M3 - Article
C2 - 25178952
AN - SCOPUS:84907339245
SN - 2041-1723
VL - 5
JO - Nature communications
JF - Nature communications
M1 - 4734
ER -