The TRPV1 channel is a sensitive detector of pain-producing stimuli, including noxious heat, acid, inflammatory mediators, and vanilloid compounds. Although binding sites for some activators have been identified, the location of the temperature sensor remains elusive. Using available structures of TRPV1 and voltage-activated potassium channels, we engineered chimeras wherein transmembrane regions of TRPV1 were transplanted into the Shaker Kv channel. Here we show that transplanting the pore domain of TRPV1 into Shaker gives rise to functional channels that can be activated by a TRPV1-selective tarantula toxin that binds to the outer pore of the channel. This pore-domain chimera is permeable to Na⁺, K⁺, and Ca²⁺ ions, and remarkably, is also robustly activated by noxious heat. Our results demonstrate that the pore of TRPV1 is a transportable domain that contains the structural elements sufficient for activation by noxious heat.

中文翻译：

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热激活是TRPV1的孔域固有的

TRPV1通道是敏感的疼痛产生刺激物检测器，包括有害热量，酸，炎性介质和香草类化合物。尽管已经确定了一些激活剂的结合位点，但是温度传感器的位置仍然难以捉摸。利用TRPV1和电压激活钾通道的可用结构，我们设计了嵌合体，其中TRPV1的跨膜区被移植到Shaker Kv通道中。在这里，我们显示将TRPV1的孔结构域移植到Shaker中会产生功能性通道，该通道可以由结合通道外孔的TRPV1选择性狼蛛毒素激活。该孔域嵌合体可渗透Na ⁺，K ⁺和Ca ²⁺有害的离子还显着地激活了离子。我们的结果表明，TRPV1的孔是一个可运输的区域，其中包含足以被有毒的热量激活的结构元素。