TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour.
TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour.
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DOI：
10.1038/ncomms5734
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发表时间：
2014-09-02
影响因子：
16.6
通讯作者：
Liedtke, Wolfgang B.
中科院分区：
文献类型：
--
作者：
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.
动物需要感知潜在的危险环境并做出反应。在大多数动物中，Trp离子通道可能通过钙离子内流参与伤害性感受。然而，离子渗透与动物文明行为之间的关系尚不清楚。在这里，我们使用了一个与哺乳动物疼痛相关的无脊椎动物模型。我们分析了TRPV通道OSM-9在秀丽线虫渗透回避行为中可能的选择性过滤器。利用在头部伤害性感受器神经元ASH中表达的诱变的OSM-9，我们研究了伤害性行为和钙内流。在选择性过滤器M601-F609、Y604G中，显著减少了回避行为，消除了钙离子瞬变。Y604F还取消了ASH中的钙瞬变，同时维持了回避行为，但它破坏了行为可塑性。OSM-9孔的同源模拟表明，Y604可能起到支架作用。因此，OSM-9选择性过滤器中的芳香族残留物对疼痛行为和离子渗透至关重要。这些发现对于理解哺乳动物伤害性感受的进化根源具有重要意义。TRP是钙渗透通道，参与感知破坏性刺激，但钙内流与疼痛行为之间的关系一直难以捉摸。在这里，作者发现色氨酸通道OSM-9在线虫体内作为离子通道发挥作用，并建立对蠕虫疼痛样行为至关重要的残基。
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. TRPs are calcium-permeable channels involved in the sensing of damaging stimuli but the relationship between calcium influx and pain behaviour has been elusive. Here the authors find that the TRP channel OSM-9 functions as an ion channel in vivo in C. elegans, and establish residues that are critical for worm pain-like behaviour.
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影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
7.4
作者：
Chen Y;Williams SH;McNulty AL;Hong JH;Lee SH;Rothfusz NE;Parekh PK;Moore C;Gereau RW 4th;Taylor AB;Wang F;Guilak F;Liedtke W
通讯作者：
Liedtke W
DOI：
10.1523/jneurosci.0497-10.2010
发表时间：
2010-06-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Harris G;Mills H;Wragg R;Hapiak V;Castelletto M;Korchnak A;Komuniecki RW
通讯作者：
Komuniecki RW
影响因子：
5.3
作者：
Hapiak, Vera;Summers, Philip;Komuniecki, Richard
通讯作者：
Komuniecki, Richard
影响因子：
25
作者：
Grandl, Joerg;Hu, Hongzhen;Bandell, Michael;Bursulaya, Badry;Schmidt, Manuela;Petrus, Matt;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem