Hysteresis of gating underlines sensitization of TRPV3 channels.
Hysteresis of gating underlines sensitization of TRPV3 channels.
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DOI：
10.1085/jgp.201110689
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Qin F
中科院分区：
文献类型：
--
作者：
Liu B;Yao J;Zhu MX;Qin F
瞬时受体电位家族的香草酸受体在热感觉和伤害感受中具有功能。其中，瞬时受体电位香草酸（TRPV）3显示出一种独特的性质，通过这种性质，反复刺激会导致其活性连续增加。该特性被称为致敏，并且在天然细胞和异源表达TRPV 3的细胞中均观察到。细胞内钙离子水平的瞬时升高通过介导钙调蛋白与通道的相互作用而在这一过程中发挥关键作用。在支持的机制，BAPTA，快速钙螯合剂，加速敏化，而缓慢螯合剂EGTA是无效的。在这里，我们表明TRPV3的敏化作用也独立于Ca2+发生。在由内向外和由外向外的膜贴片中均观察到。BAPTA而不是EGTA对通道激活具有直接增强作用。缺乏Ca2+缓冲能力的BAPTA类似物同样有效。刺激诱导的增敏作用和BAPTA的增强作用在可逆性上是不同的。我们得出结论，TRPV3的敏化是固有的通道本身，并发生作为通道门控滞后的结果。BAPTA通过增强通道的门控来加速敏化过程。
Vanilloid receptors of the transient receptor potential family have functions in thermal sensation and nociception. Among them, transient receptor potential vanilloid (TRPV)3 displays a unique property by which the repeated stimulation causes successive increases in its activity. The property has been known as sensitization and is observed in both native cells and cells heterologously expressing TRPV3. Transient increases in intracellular calcium levels have been implicated to play a key role in this process by mediating interaction of calmodulin with the channel. In support of the mechanism, BAPTA, a fast calcium chelator, accelerates the sensitization, whereas the slow chelator EGTA is ineffectual. Here, we show that the sensitization of TRPV3 also occurred independently of Ca2+. It was observed in both inside-out and outside-out membrane patches. BAPTA, but not EGTA, has a direct potentiation effect on channel activation. Analogues of BAPTA lacking Ca2+-buffering capability were similarly effective. The stimulation-induced sensitization and the potentiation by BAPTA are distinguishable in reversibility. We conclude that the sensitization of TRPV3 is intrinsic to the channel itself and occurs as a result of hysteresis of channel gating. BAPTA accelerates the sensitization process by potentiating the gating of the channel.
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