Impaired pressure sensation in mice lacking TRPV4
Impaired pressure sensation in mice lacking TRPV4
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DOI：
10.1074/jbc.m302561200
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发表时间：
2003-06-20
影响因子：
4.8
通讯作者：
Imai, M
中科院分区：
文献类型：
--
作者：
Suzuki, M;Mizuno, A;Imai, M
脊椎动物的压力感，即机械感觉，在分子水平上仍然知之甚少。离子通道TRPV4属于色氨酸家族，是机械敏感性钙离子通透通道的候选者。位于背根神经节内。在目前的研究中，我们发现破坏小鼠的TRPV4基因显著降低了尾巴对压力和酸性伤害性的敏感性。对伤害性刺激的反应阈值和对刺激反应的有髓神经传导速度也受到损害。未检测到无髓神经激活。然而，老鼠仍然保留了嗅觉、味觉和避热功能。中国仓鼠卵巢细胞体外表达的TRPV4通道可被低pH、柠檬酸和膨胀剂开放，但不能被热或辣椒素开放。这些数据表明，TRPV4通道对于正常的压力检测是必不可少的，并且是高阈值机械感觉复合体的受体。
The sensation of pressure, mechanosensation, in vertebrates remains poorly understood on the molecular level. The ion channel TRPV4 is in the TRP family and is a candidate for a mechanosensitive calcium-permeable channel. It is located in dorsal root ganglia. In the present study, we show that disrupting the Trpv4 gene in mice markedly reduced the sensitivity of the tail to pressure and acidic nociception. The threshold to noxious stimuli and the conduction velocity of myelinated nerve responding to stimuli were also impaired. Activation of unmyelinated nerve was undetected. However, the mouse still retained olfaction, taste sensation, and heat avoidance. The TRPV4 channel expressed in vitro in Chinese hamster ovary cells was opened by low pH, citrate, and inflation but not by heat or capsaicin. These data identify the TRPV4 channel as essential for the normal detection of pressure and as a receptor of the high-threshold mechanosensory complex.