Heat-Evoked Activation of the Ion Channel, TRPV4
Heat-Evoked Activation of the Ion Channel, TRPV4
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DOI：
10.1523/jneurosci.22-15-06408.2002
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发表时间：
2002-08
期刊：
影响因子：
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通讯作者：
A. D. Güler;Hyosang Lee;Tohko Iida;I. Shimizu;M. Tominaga;M. Caterina
中科院分区：
文献类型：
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作者：
A. D. Güler;Hyosang Lee;Tohko Iida;I. Shimizu;M. Tominaga;M. Caterina
哺乳动物的神经系统不断评估内部和环境的温度，以维持体内平衡，避免极端的温度。瞬时受体电位(TRP)家族中的几个成员被认为是热刺激的转导，包括被热激活的TRPV1和TRPV2，以及被冷激活的TRPM8。在这里，我们证明了Trp家族的另一个成员，TRPV4，以前被描述为低渗透压激活的离子通道，也可以被热激活。在温度升高的情况下，TRPV4介导非洲爪哇卵母细胞的大内向电流，以及内向电流和钙离子流入人胚胎肾293细胞。在这两种情况下，这些反应都是在低于激活TRPV1所需的温度下观察到的，并且可以被Ru红可逆地抑制。热诱发的TRPV4介导的反应在低渗溶液中较大，在高渗透溶液中较低。与这些功能特性一致，我们观察到下丘脑前部结构中的TRPV4免疫反应阳性，参与温度感觉和热信息和渗透信息的整合。总而言之，这些数据暗示TRPV4可能是下丘脑内热刺激的传送器。
The mammalian nervous system constantly evaluates internal and environmental temperatures to maintain homeostasis and to avoid thermal extremes. Several members of the transient receptor potential (TRP) family of ion channels have been implicated as transducers of thermal stimuli, including TRPV1 and TRPV2, which are activated by heat, and TRPM8, which is activated by cold. Here we demonstrate that another member of the TRP family, TRPV4, previously described as a hypo-osmolarity-activated ion channel, also can be activated by heat. In response to warm temperatures, TRPV4 mediates large inward currents in Xenopus oocytes and both inward currents and calcium influx into human embryonic kidney 293 cells. In both cases these responses are observed at temperatures lower than those required to activate TRPV1 and can be inhibited reversibly by ruthenium red. Heat-evoked TRPV4-mediated responses are greater in hypo-osmotic solutions and reduced in hyperosmotic solutions. Consistent with these functional properties, we observed TRPV4 immunoreactivity in anterior hypothalamic structures involved in temperature sensation and the integration of thermal and osmotic information. Together, these data implicate TRPV4 as a possible transducer of warm stimuli within the hypothalamus.