Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2
Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2
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DOI：
10.1016/j.bpj.2016.03.005
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发表时间：
2016-04-12
影响因子：
3.4
通讯作者：
Qin, Feng
中科院分区：
文献类型：
--
作者：
Liu, Beiying;Qin, Feng
热TRP通道介导温度传导和痛觉。香草素受体TRPV2参与检测高阈值伤害感受器亚群中的有害热。它在热痛觉过敏的发生发展中也起着关键作用，但其潜在机制仍不清楚。在这里，我们分析TRPV2通道的热敏感性。通道的热激活表现出强烈的使用依赖性。先前的热激活可以深刻地改变其随后的温度响应性，导致温度激活阈值和温度依赖性的斜率敏感性降低，同时加速激活时间过程。值得注意的是，热和激动剂激活在交叉使用依赖性方面不同。先前的热刺激可以显著地敏化激动剂反应，但反之亦然。定量分析表明，热灵敏度的使用依赖性与通道的温度传感过程有关。TRPV 2的使用依赖性揭示了该通道可以具有动态温度敏感性。通道内的温度感测结构具有多种构象，并且温度激活途径与激动剂激活途径分开。在生理学上，TRPV 2的使用依赖性赋予伤害感受器对热的超敏性，从而提供外周热痛觉过敏的机制。
Thermal TRP channels mediate temperature transduction and pain sensation. The vanilloid receptor TRPV2 is involved in detection of noxious heat in a subpopulation of high-threshold nociceptors. It also plays a critical role in development of thermal hyperalgesia, but the underlying mechanism remains uncertain. Here we analyze the heat sensitivity of the TRPV2 channel. Heat activation of the channel exhibits strong use dependence. Prior heat activation can profoundly alter its subsequent temperature responsiveness, causing decreases in both temperature activation threshold and slope sensitivity of temperature dependence while accelerating activation time courses. Notably, heat and agonist activations differ in cross use-dependence. Prior heat stimulation can dramatically sensitize agonist responses, but not conversely. Quantitative analyses indicate that the use dependence in heat sensitivity is pertinent to the process of temperature sensing by the channel. The use dependence of TRPV2 reveals that the channel can have a dynamic temperature sensitivity. The temperature sensing structures within the channel have multiple conformations and the temperature activation pathway is separate from the agonist activation pathway. Physiologically, the use dependence of TRPV2 confers nociceptors with a hypersensitivity to heat and thus provides a mechanism for peripheral thermal hyperalgesia.