The biophysical and molecular basis of TRPV1 proton gating
The biophysical and molecular basis of TRPV1 proton gating
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DOI：
10.1038/emboj.2011.19
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发表时间：
2011-03-16
期刊：
影响因子：
11.4
通讯作者：
Grimm, Christian
中科院分区：
文献类型：
--
作者：
Aneiros, Eduardo;Cao, Lishuang;Grimm, Christian
辣椒素受体TRPV1是非选择性阳离子通道瞬时受体潜能家族的一员，是一种多通道伤害性感受器。有毒的热刺激、质子和生物碱刺激性辣椒素打开通道。热和辣椒素激活的机制与TRPV1中的电压依赖门控有关。然而，到目前为止，人们还不清楚质子激活或增强或两者都与类似的电压依赖机制有关，以及质子门控背后的分子决定因素。利用全细胞膜片钳技术，我们证明了质子通过使激活曲线的电压依赖于更多的生理膜电位来激活和增强TRPV1。我们进一步确定了TRPV1孔区中的一个关键残基F660，它对电压依赖的质子激活和增强至关重要。我们的结论是，TRPV1的质子激活和增强都是电压依赖的，660氨基酸是质子介导的TRPV1门控所必需的。EMBO期刊(2011)30,994-1002。DOI：10.1038/Intemj.2011.19；2011年2月1日在线发布
The capsaicin receptor TRPV1, a member of the transient receptor potential family of non-selective cation channels is a polymodal nociceptor. Noxious thermal stimuli, protons, and the alkaloid irritant capsaicin open the channel. The mechanisms of heat and capsaicin activation have been linked to voltage-dependent gating in TRPV1. However, until now it was unclear whether proton activation or potentiation or both are linked to a similar voltage-dependent mechanism and which molecular determinants underlie the proton gating. Using the whole-cell patch-clamp technique, we show that protons activate and potentiate TRPV1 by shifting the voltage dependence of the activation curves towards more physiological membrane potentials. We further identified a key residue within the pore region of TRPV1, F660, to be critical for voltage-dependent proton activation and potentiation. We conclude that proton activation and potentiation of TRPV1 are both voltage dependent and that amino acid 660 is essential for proton-mediated gating of TRPV1. The EMBO Journal (2011) 30, 994-1002. doi: 10.1038/emboj.2011.19; Published online 1 February 2011