Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin
Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin
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DOI：
10.1126/science.1108609
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发表时间：
2005-03-04
期刊：
影响因子：
56.9
通讯作者：
Patapoutian, A
中科院分区：
文献类型：
--
作者：
Moqrich, A;Hwang, SW;Patapoutian, A
环境温度被认为是神经元通过它们在皮肤中的投射直接感觉到的。哺乳动物瞬时受体电位(Trp)家族离子通道的一个子集参与了这一过程。这些“热TRPs”在不同的温度阈值下被激活，通常在感觉神经元中表达。TRPV3被热(33℃)激活，与大多数热TRP不同的是，它在小鼠角质形成细胞中表达。我们发现，TRPV3缺失的小鼠对无害和有害的热有强烈的反应缺陷，但在其他感觉方式上没有；因此，TRPV3在温度感觉中具有特定的作用。天然化合物樟脑，调节人类的温暖感觉，被证明是TRPV3的一种特殊激活剂。樟脑能激活原代培养的角质形成细胞，但不能激活感觉神经元，这种活性在TRPV3基因缺失的小鼠中被取消。因此，角质形成细胞上的热激活受体在哺乳动物体温调节中起着重要作用。
Environmental temperature is thought to be directly sensed by neurons through their projections in the skin. A subset of the mammalian transient receptor potential (TRP) family of ion channels has been implicated in this process. These "thermoTRPs" are activated at distinct temperature thresholds and are typically expressed in sensory neurons. TRPV3 is activated by heat (>33degreesC) and, unlike most thermoTRPs, is expressed in mouse keratinocytes. We found that TRPV3 null mice have strong deficits in responses to innocuous and noxious heat but not in other sensory modalities; hence, TRPV3 has a specific role in thermosensation. The natural compound camphor, which modulates sensations of warmth in humans, proved to be a specific activator of TRPV3. Camphor activated cultured primary keratinocytes but not sensory neurons, and this activity was abolished in TRPV3 null mice. Therefore, heat-activated receptors in keratinocytes are important for mammalian thermosensation.