Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 4734 |
| Journal | Nature Communications |
| Volume | 5 |
| DOIs | |
| State | Published - Sep 2 2014 |
Fingerprint
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Chemistry(all)
- Physics and Astronomy(all)
Cite this
TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour. / 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.
In: Nature Communications, Vol. 5, 4734, 02.09.2014.Research output: Contribution to journal › Article
}
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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84907339245&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907339245&partnerID=8YFLogxK
U2 - 10.1038/ncomms5734
DO - 10.1038/ncomms5734
M3 - Article
VL - 5
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 4734
ER -