TRP channels of the transient receptor potential ion channel superfamily are involved in a wide variety of mechanosensory processes, including touch sensation, pain, blood pressure regulation, bone loading and detection of cerebrospinal fluid flow. However, in many instances it is unclear whether TRP channels are the primary transducers of mechanical force in these processes. In this study, we tested stretch activation of eleven TRP channels from six mammalian subfamilies. We found that these TRP channels were insensitive to short membrane stretches in cellular systems. Furthermore, we purified TRPC6 and demonstrated its insensitivity to stretch in liposomes, an artificial bilayer system free from cellular components. Additionally, we demonstrated that, when expressed in C. elegans neurons, mouse TRPC6 restores the mechanoresponse of a touch insensitive mutant but requires diacylglycerol for activation. These results strongly suggest that the mammalian members of the TRP ion channel family are insensitive to tension induced by cell membrane stretching and, thus, are more likely to be activated by cytoplasmic tethers or downstream components and to act as amplifiers of cellular mechanosensory signaling cascades.

中文翻译：

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哺乳动物TRP离子通道对膜拉伸不敏感。

瞬时受体电位离子通道超家族的TRP通道涉及多种机械感觉过程，包括触觉，疼痛，血压调节，骨负荷和脑脊液流量检测。但是，在许多情况下，尚不清楚在这些过程中，TRP通道是否是机械力的主要传感器。在这项研究中，我们测试了来自六个哺乳动物亚家族的11个TRP通道的拉伸激活。我们发现这些TRP通道对细胞系统中的短膜拉伸不敏感。此外，我们纯化了TRPC6，并证明了它对脂质体的不敏感性，脂质体是一种不含细胞成分的人工双层系统。此外，我们证明了当在秀丽隐杆线虫神经元中表达时，小鼠TRPC6恢复了对触摸不敏感的突变体的机械响应，但需要使用二酰基甘油进行激活。这些结果强烈表明，TRP离子通道家族的哺乳动物成员对细胞膜拉伸诱导的张力不敏感，因此更可能被细胞质系链或下游成分激活，并充当细胞机械感觉信号级联反应的扩增子。