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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Trpa1 Acts As A Cold Sensor In Vitro And In Vivo
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Trpa1 Acts As A Cold Sensor In Vitro And In Vivo

机译：Trpa1充当体内和体外的冷传感器

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摘要

TRPA1 functions as an excitatory ionotropic receptor in sensory neurons. It was originally described as a noxious cold-activated channel, but its cold sensitivity has been disputed in later studies, and the contribution of TRPA1 to thermosensing is currently a matter of strong debate. Here, we provide several lines of evidence to establish that TRPA1 acts as a cold sensor in vitro and in vivo. First, we demonstrate that heterologously expressed TRPA1 is activated by cold in a Ca~(2+)-independent and Ca~(2+) store-independent manner; temperature-dependent gating of TRPA1 is mechanistically analogous to that of other temperature-sensitive TRP channels, and it is preserved after treatment with the TRPA1 agonist mustard oil. Second, we identify and characterize a specific subset of cold-sensitive trigeminal ganglion neurons that is absent in TRPA1-deficient mice. Finally, cold plate and tail-flick experiments reveal TRPA1 -dependent, cold-induced nociceptive behavior in mice. We conclude that TRPA1 acts as a major sensor for noxious cold.
机译：TRPA1充当感觉神经元中的兴奋性离子受体。它最初被描述为一种有害的冷激活通道，但其冷敏性在后来的研究中受到争议，而TRPA1对热敏的贡献目前是一个有争议的问题。在这里，我们提供了几条证据来证明TRPA1在体外和体内均起着感冒传感器的作用。首先，我们证明异源表达的TRPA1通过冷以Ca〜（2+）独立和Ca〜（2+）存储独立方式激活。从机理上讲，TRPA1的依赖温度的门控机制与其他对温度敏感的TRP通道的门控机制类似，并且在用TRPA1激动剂芥子油处理后得以保留。第二，我们确定并表征在TRPA1缺陷型小鼠中不存在的冷敏三叉神经节神经元的特定子集。最后，冷板和甩尾实验揭示了TRPA1依赖性的，冷诱导的小鼠伤害性行为。我们得出的结论是TRPA1充当了有害感冒的主要传感器。

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