The TRPM2 ion channel is required for sensitivity to warmth.
The TRPM2 ion channel is required for sensitivity to warmth.
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DOI：
10.1038/nature19074
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发表时间：
2016-08-25
期刊：
影响因子：
64.8
通讯作者：
McNaughton PA
中科院分区：
文献类型：
--
作者：
Tan CH;McNaughton PA
我们如何感受到温暖？在体感神经元中表达的热激活离子通道检测从极端热(TRPV2)、痛苦热(TRPV1、TRPM3、ANO1)、非痛苦温暖(TRPV3和TRPV4)、非痛苦凉爽(TRPM8)到痛苦寒冷(TRPA1)的整个温度范围。然而，这些离子通道中的每一个的基因缺失对小鼠的热行为只有轻微的影响，除了TRPM8，它的缺失对10°C-25°C范围内适度凉爽的感知有显著影响。在这里，我们使用钙成像来识别一组新的热敏感体感神经元，这些神经元不表达任何已知的热激活Trp通道。然后，我们使用钙成像、电生理学和RNA测序的组合来证明在这些神经元中产生热敏感性的离子通道是TRPM2。自主神经通常被认为是唯一的运动，也表达TRPM2并直接对热做出反应。在TRPM2基因缺失的小鼠中，它们对无害的温暖温度的感觉出现了显著的缺陷，这与TRPM2启动了驱动求凉行为的“温暖”信号的想法一致。
How do we detect warmth? Thermally-activated ion channels expressed in somatosensory neurons detect the entire thermal range from extreme heat (TRPV2), painful heat (TRPV1, TRPM3, ANO1), non-painful warmth (TRPV3 and TRPV4) and non-painful coolness (TRPM8) through to painful cold (TRPA1). Genetic deletion of each of these ion channels, however, has only modest effects on thermal behaviour in mice, with the exception of TRPM8, whose deletion has marked effects on the perception of moderate coolness in the range 10°C - 25°C. The molecular mechanism responsible for detecting non-painful warmth, in particular, is unresolved. Here we used calcium imaging to identify a population of novel thermally-sensitive somatosensory neurons which do not express any of the known thermally-activated TRP channels. We then used a combination of calcium imaging, electrophysiology and RNA sequencing to show that the ion channel generating heat sensitivity in these neurons is TRPM2. Autonomic neurons, usually thought of as exclusively motor, also express TRPM2 and respond directly to heat. Mice in which TRPM2 had been genetically deleted showed a striking deficit in their sensation of non-noxious warm temperatures, consistent with the idea that TRPM2 initiates a “warm” signal which drives cool-seeking behaviour.
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