来自Scripps研究院(The Scripps Research Institute,TSRI)和诺华研究基金会基因组学研究院(Genomics Institute of the Novartis Research Foundation ,GNF)的一组研究人员识别并复制出皮肤细胞用于感觉冷温的基因。
由Ardem Patapoutian领导的研究小组描述了该基因编码的蛋白质:一种称为TRPM8的TRP(transient receptor potential)型通道。这个膜蛋白感觉到一定温度时就会打开,使离子通过,产生发送到大脑的电信号。
Patapoutian 的小组第一次提出TRPM8是控制冷的感觉的关键基因。为了测试这个假说,研究小组观察基因经过修改,而缺乏响应冷刺激的基因之小鼠的行为变化。
TRPM8正常的小鼠可以感觉到冷的温度,而朝向较温暖的地区移动。没有TRPM8的小鼠对于摄氏18 到31度的温度范围并无偏好,显示牠们无法感觉到这个温度范围。
在进一步的研究中,缺少TRPM8的小鼠对于-1℃的冰冷板并无感觉能力。这项研究发表于5月3 日的Neuron中, TRPM8 的冷的活化作用可与一些利用冷觉的止痛药有关,例如薄荷。
(编译/姜欣慧) (资料来源 : Bio.com)
英文原文链接:
原始出处:
Neuron, Vol 54, 371-378, 03 May 2007
Report
TRPM8 Is Required for Cold Sensation in Mice
Ajay Dhaka,1 Amber N. Murray,1 Jayanti Mathur,2 Taryn J. Earley,1 Matt J. Petrus,2 and Ardem Patapoutian1,2,
1 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
2 Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA
Corresponding author
Ardem Patapoutian
apatapou@gnf.org
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.