TRPV3 is a calcium-permeable temperature-sensitive cation channel

TRPV3 is a calcium-permeable temperature-sensitive cation channel
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DOI:
10.1038/nature00882
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发表时间:
2002-07-11
期刊:
影响因子:
64.8
通讯作者:
Clapham, DE
Clapham, DE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Xu, HX;Ramsey, IS;Clapham, DE

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瞬时受体电位(Trp)蛋白是阳离子选择性通道,在感觉和血管调节等不同过程中发挥作用。由热和辣椒素控制的哺乳动物色氨酸通道(>43℃;TRPV1(参考文献)1)),毒热(>52℃;TRPV2(参考文献)2))和冷却(<22℃;TRPM8(参考文献3,4))已被克隆;然而,在类似于22摄氏度到40摄氏度的范围内,关于温度感知的分子决定因素知之甚少。我们鉴定了香草样通道家族的一个成员,人TRPV3(HTRPV3),它在皮肤、舌头、背根神经节、三叉神经节、脊髓和脑中表达。在转hTRPV3的哺乳动物细胞中,将温度从22摄氏度提高到40摄氏度,通过激活非选择性的阳离子电导来提高细胞内钙离子。在已发表的感觉神经元记录中,电流强烈依赖于温度,通过反复加热而敏化,并在加热和冷却时表现出明显的滞后(5-10)。基于这些性质,我们认为hTRPV3在TRPM8和TRPV1之间的生理温度范围内是温度敏感的。
Transient receptor potential (TRP) proteins are cation-selective channels that function in processes as diverse as sensation and vasoregulation. Mammalian TRP channels that are gated by heat and capsaicin (> 43 degreesC; TRPV1 (ref. 1)), noxious heat (> 52 degreesC; TRPV2 (ref. 2)), and cooling (< 22 degrees C; TRPM8 (refs 3, 4)) have been cloned; however, little is known about the molecular determinants of temperature sensing in the range between similar to 22 degrees C and 40 degrees C. Here we have identified a member of the vanilloid channel family, human TRPV3 (hTRPV3) that is expressed in skin, tongue, dorsal root ganglion, trigeminal ganglion, spinal cord and brain. Increasing temperature from 22 degrees C to 40 degrees C in mammalian cells transfected with hTRPV3 elevated intracellular calcium by activating a nonselective cationic conductance. As in published recordings from sensory neurons, the current was steeply dependent on temperature, sensitized with repeated heating, and displayed a marked hysteresis on heating and cooling(5-10). On the basis of these properties, we propose that hTRPV3 is thermosensitive in the physiological range of temperatures between TRPM8 and TRPV1.