Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing
Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing
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DOI：
10.1523/jneurosci.0013-05.2005
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发表时间：
2005-04-20
影响因子：
5.3
通讯作者：
García-Añoveros, J
中科院分区：
文献类型：
--
作者：
Nagata, K;Duggan, A;García-Añoveros, J
感觉细胞的机械感觉通道介导听觉、触觉和某些形式的疼痛的感觉。 TRPA1（离子通道蛋白 TRP 家族的成员）通道被产生疼痛的化学物质激活，其抑制会损害毛细胞的机械转导。如本文和之前所示，TRPA1 由毛细胞以及大多数伤害感受器（背根、三叉神经节和结状神经节的小神经元）表达，并定位于它们的感觉末梢（分别为机械感觉立体纤毛和外周游离神经）。因此，TRPA1 通道被认为介导毛细胞和伤害感受器的转导。因此，我们发现异源表达的 TRPA1 显示听觉和伤害感受传感器预期的通道行为。首先，TRPA1 和毛细胞传感器共享一组独特的孔特性，没有任何其他通道描述过（被钆、阿米洛利、庆大霉素和钌红阻断，电导范围类似于 100 pS，被钙降低到 54%，渗透钙诱导的增强，然后关闭，并通过去极化重新打开），支持 TRPA1 作为毛细胞的孔形成亚基的直接作用换能器。其次，TRPA1 通道在超极化细胞中失活，但在去极化细胞中保持开放。这一特性提供了一种缺乏脱敏、重合检测和异常性疼痛的机制，这些机制通过允许感觉神经元不断地对阈值上（即有害）的持续刺激做出反应，同时允许同一细胞忽略阈下（即无害）的持续刺激来表征疼痛。我们的结果支持 TRPA1 在伤害感受器和毛细胞转导中的作用。
Mechanosensory channels of sensory cells mediate the sensations of hearing, touch, and some forms of pain. The TRPA1 (a member of the TRP family of ion channel proteins) channel is activated by pain-producing chemicals, and its inhibition impairs hair cell mechanotransduction. As shown here and previously, TRPA1 is expressed by hair cells as well as by most nociceptors (small neurons of dorsal root, trigeminal, and nodose ganglia) and localizes to their sensory terminals (mechanosensory stereocilia and peripheral free nerves, respectively). Thus, TRPA1 channels are proposed to mediate transduction in both hair cells and nociceptors. Accordingly, we find that heterologously expressed TRPA1 display channel behaviors expected for both auditory and nociceptive transducers. First, TRPA1 and the hair cell transducer share a unique set of pore properties not described for any other channel (block by gadolinium, amiloride, gentamicin, and ruthenium red, a ranging conductance of similar to 100 pS that is reduced to 54% by calcium, permeating calcium-induced potentiation followed by closure, and reopening by depolarization), supporting a direct role of TRPA1 as a pore-forming subunit of the hair cell transducer. Second, TRPA1 channels inactivate in hyperpolarized cells but remain open in depolarized cells. This property provides a mechanism for the lack of desensitization, coincidence detection, and allodynia that characterize pain by allowing a sensory neuron to respond constantly to sustained stimulation that is suprathreshold (i.e., noxious) and yet permitting the same cell to ignore sustained stimulation that is subthreshold (i.e., innocuous). Our results support a TRPA1 role in both nociceptor and hair cell transduction.