TRPV3 and TRPV4 mediate warmth-evoked currents in primary mouse keratinocytes

TRPV3 and TRPV4 mediate warmth-evoked currents in primary mouse keratinocytes
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DOI:
10.1074/jbc.m401872200
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发表时间:
2004-05-14
影响因子:
4.8
通讯作者:
Caterina, MJ
Caterina, MJ
中科院分区:
生物学2区
文献类型:
--
作者:
Chung, MK;Lee, H;Caterina, MJ

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最近,在哺乳动物和非哺乳动物物种中发现了一个温度激活离子通道家族,它们似乎有助于温度感觉。这些蛋白质中的两种,TRPV3和TRPV4,是通过环境温度的适度升高激活的离子通道。定位研究表明,这两种蛋白质,除了在感觉神经元中表达,也在皮肤角质形成细胞中表达。这些和其他研究结果表明,角质形成细胞可能与感觉神经元一起感知我们的热环境。在这项研究中,我们证明了从小鼠皮肤中分离的原代角质形成细胞表现出两种不同的热诱发电流反应,在环境温度的温和增加。这些反应类型中更常见的与重组TRPV4介导的反应具有相当大的相似性,在缺乏该离子通道的小鼠中不存在,并且在TRPV4重新引入后恢复。第二,罕见的反应强烈类似于那些由重组TRPV3介导的。总之,这些发现表明,角质形成细胞确实可以作为热敏细胞,他们这样做,通过至少两个不同的转导机制。
Recently, a family of temperature-activated ion channels has been identified in mammalian and nonmammalian species that appear to contribute to thermosensation. Two of these proteins, TRPV3 and TRPV4, are ion channels activated by modest increases in ambient temperature. Localization studies have indicated that both proteins, in addition to being expressed in sensory neurons, are also expressed in skin keratinocytes. These and other findings have suggested that keratinocytes might act in concert with sensory neurons to perceive our thermal environment. In this study, we demonstrate that primary keratinocytes isolated from mouse skin exhibit two distinct heat-evoked current responses to mild increases in ambient temperature. The more common of these response types bears considerable similarity to responses mediated by recombinant TRPV4, is absent in mice lacking this ion channel, and is restored upon TRPV4 reintroduction. The second, rarer response strongly resembles those mediated by recombinant TRPV3. Together, these findings demonstrate that keratinocytes can indeed act as thermosensory cells and that they do so via at least two distinct transduction mechanisms.