High temperature sensitivity is intrinsic to voltage-gated potassium channels.
High temperature sensitivity is intrinsic to voltage-gated potassium channels.
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DOI：
10.7554/elife.03255
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发表时间：
2014-07-16
期刊：
影响因子：
7.7
通讯作者：
Zheng J
中科院分区：
文献类型：
--
作者：
Yang F;Zheng J
温度敏感的瞬时受体电位（TRP）离子通道是大的四聚体阳离子通道超家族的成员，但被认为是唯一对热敏感的，这被推测是由于存在未鉴定的温度敏感域。在这里，我们报告说，同源电压门控钾（KV）通道也表现出高的温度敏感性相媲美的TRPV 1，这是在特定条件下检测时，电压传感器是通过内在机制或突变的激活门功能去耦。有趣的是，突变可以将Shaker通道调节为热激活或热失活。因此，高温度敏感性是TRP和Kv通道的固有特性。我们的研究结果表明，重要的生理作用，热诱导的变化KV通道活动。从机制上讲，我们的研究结果表明，温度敏感TRP通道可能不包含一个专门的热传感器域，相反，非强制性变构门控允许内在的热敏性驱动通道激活，允许温度敏感TRP通道作为多模态伤害感受器。http://dx.doi.org/10.7554/eLife.03255.001如果你触摸太热的东西，它会导致你疼痛并损伤你的皮肤。至少在一定程度上，由于被称为温度敏感TRP离子通道的蛋白质，感知物体发出的热量或环境温度是可能的。这些蛋白质存在于皮肤下神经末梢的细胞膜中;它们对热量做出反应，允许离子流入神经细胞。这反过来又触发了一种神经冲动，被发送到我们的中枢神经系统，并被感知为热和/或疼痛。感觉热的能力被认为是这些TRP离子通道所独有的，并且人们认为这些离子通道包含尚未鉴定的温度感应域。然而，Yang和Zheng现在报告说，类似的离子通道，响应细胞膜上存在的电压变化而打开，也对温度变化敏感。这些“电压门控通道”的温度响应在过去很大程度上避开了研究人员的注意。这是因为离子通道的某些部分就像一个“电压传感器”，只有当膜电压改变时才会移动，通常情况下离子通道保持关闭，而当离子通道移动时，离子通道直接打开。像所有其他蛋白质一样，离子通道是由称为氨基酸的较小的构建模块组成的;通过改变电压门控通道中的一些氨基酸，杨和郑可以解除这些正常连接的作用。通道的变化意味着当电压传感器移动时，它不会立即打开;降低细胞内钙离子的浓度与改变这些氨基酸具有相同的效果。这两种方法都表明，在膜电压的变化导致电压传感器移动后，离子通道保持关闭，直到高温导致它打开。Yang和Zheng揭示了修饰的电压门控通道对温度的反应与典型的热敏TRP离子通道相当。进一步的实验表明，用不同的氨基酸取代电压门控钾离子通道中的一些氨基酸，可以导致通道被热打开或关闭。Yang和Zheng的发现表明，温度敏感TRP通道可能不包含专门的热传感器域。相反，由于这些TRP离子通道不需要蛋白质的其他部分移动以打开通道，因此它们可以通过自身固有的对热的敏感性被激活。DOI：http://dx.doi.org/10.7554/eLife.03255.002网站
Temperature-sensitive transient receptor potential (TRP) ion channels are members of the large tetrameric cation channels superfamily but are considered to be uniquely sensitive to heat, which has been presumed to be due to the existence of an unidentified temperature-sensing domain. Here we report that the homologous voltage-gated potassium (Kv) channels also exhibit high temperature sensitivity comparable to that of TRPV1, which is detectable under specific conditions when the voltage sensor is functionally decoupled from the activation gate through either intrinsic mechanisms or mutations. Interestingly, mutations could tune Shaker channel to be either heat-activated or heat-deactivated. Therefore, high temperature sensitivity is intrinsic to both TRP and Kv channels. Our findings suggest important physiological roles of heat-induced variation in Kv channel activities. Mechanistically our findings indicate that temperature-sensing TRP channels may not contain a specialized heat-sensor domain; instead, non-obligatory allosteric gating permits the intrinsic heat sensitivity to drive channel activation, allowing temperature-sensitive TRP channels to function as polymodal nociceptors. DOI: http://dx.doi.org/10.7554/eLife.03255.001 If you touch something too hot, it can cause you pain and damage your skin. Sensing the heat given off by an object or the temperature of the environment is possible, at least in part, because of proteins called temperature-sensitive TRP ion channels. These proteins are found in the cell membranes of nerve endings that are underneath the skin; and they open in response to heat, allowing ions to flow into the nerve cell. This in turn triggers a nerve impulse that is sent to our central nervous system and is perceived as heat and/or pain. The ability to sense heat was thought to be unique to these TRP ion channels, and it was believed that these ion channels contained an as-yet unidentified temperature-sensing domain. However, Yang and Zheng now report that similar ion channels, which open in response to changes in the voltage that exists across a cell's membrane, are also sensitive to changes in temperature. The temperature response of these ‘voltage-gated channels’ had largely eluded the attention of researchers in the past. This is because parts of the ion channel—which act like a ‘voltage sensor’ and only shift when the membrane voltage changes—normally keep the channel closed and directly open the channel when they move. Like all other proteins, ion channels are made from smaller building blocks called amino acids; and by changing some of the amino acids in the voltage-gated channel Yang and Zheng could decouple these normally linked actions. The changes to the channel meant that it did not immediately open when the voltage sensor moved; and decreasing the concentration of calcium ions inside the cell had the same effect as changing these amino acids. Both approaches revealed that, after a change in membrane voltage caused the voltage sensor to move, the ion channel remained closed until a high temperature caused it to open. Yang and Zheng revealed that the response of the modified voltage-gated channel to temperature was comparable to that of a typical heat-sensitive TRP ion channel. Further experiments showed that replacing some of the amino acids in the voltage-gated potassium ion channel with different amino acids could cause the channel to be either opened or closed by heat. The findings of Yang and Zheng indicate that temperature-sensing TRP channels may not contain a specialized heat-sensor domain. Instead, as these TRP ion channels do not require other parts of the protein to move in order to open the channel, they can be activated by their own inherent sensitivity to heat. DOI: http://dx.doi.org/10.7554/eLife.03255.002