TRPM8 is required for cold sensation in mice
TRPM8 is required for cold sensation in mice
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DOI：
10.1016/j.neuron.2007.02.024
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发表时间：
2007-05-03
期刊：
影响因子：
16.2
通讯作者：
Patapoutian, Ardem
中科院分区：
文献类型：
--
作者：
Dhaka, Ajay;Murray, Amber N.;Patapoutian, Ardem
ThermoTRP是瞬时受体电位（TRP）阳离子通道家族的一个子集，与温度传感有关。TRPM 8和TRPA 1都被冷却激活;然而，尚不清楚体内温度感觉是否需要任何离子通道。我们发现，缺乏TRPM 8的小鼠对冷刺激有严重的行为缺陷。在温度梯度的趋热性测定和两个温度选择测定中，TRPM 8缺陷小鼠表现出对寒冷温度的回避显著减少。TRPM 8缺陷型小鼠也缺乏对冷诱导icilin应用的行为反应，并显示出对丙酮（一种令人不快的冷刺激）的减弱反应。然而，TRPM 8缺陷小鼠对零度以下的温度具有正常的伤害性反应，这表明存在至少一种额外的有害冷受体。最后，我们表明TRPM 8介导福尔马林（一种疼痛刺激）给药后适度冷却的镇痛作用。因此，根据上下文，TRPM 8有助于感知不愉快的冷刺激或介导冷镇痛的效果。
ThermoTRPs, a subset of the Transient Receptor Potential (TRP) family of cation channels, have been implicated in sensing temperature. TRPM8 and TRPA1 are both activated by cooling; however, it is unclear whether either ion channel is required for thermosensation in vivo. We show that mice lacking TRPM8 have severe behavioral deficits in response to cold stimuli. In thermotaxis assays of temperature gradient and two-temperature choice assays, TRPM8-deficient mice exhibit strikingly reduced avoidance of cold temperatures. TRPM8-deficient mice also lack behavioral response to cold-inducing icilin application and display an attenuated response to acetone, an unpleasant cold stimulus. However, TRPM8-deficient mice have normal nociceptive-like responses to subzero centigrade temperatures, suggesting the presence of at least one additional noxious cold receptor. Finally, we show that TRPM8 mediates the analgesic effect of moderate cooling after administration of formalin, a painful stimulus. Therefore, depending on context, TRPM8 contributes to sensing unpleasant cold stimuli or mediating the effects of cold analgesia.