...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >A high-threshold heat-activated channel in cultured rat dorsal root ganglion neurons resembles TRPV2 and is blocked by gadolinium.
【24h】

A high-threshold heat-activated channel in cultured rat dorsal root ganglion neurons resembles TRPV2 and is blocked by gadolinium.

机译：培养的大鼠背根神经节神经元中的高阈值热激活通道类似于TRPV2，并被g阻断。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Heat-activated ion channels from the vanilloid-type TRP group (TRPV1-4) seem to be central for heat-sensitivity of nociceptive sensory neurons. Displaying a high-threshold (> 52 degrees C) for activation, TRPV2 was proposed to act as a sensor for intense noxious heat in mammalian sensory neurons. However, although TRPV2 is expressed in a distinct population of thinly myelinated primary afferents, a widespread expression in a variety of neuronal and non-neuronal tissues suggests a more diverse physiological role of TRPV2. In its role as a heat-sensor, TRPV2 has not been thoroughly characterized in terms of biophysical and pharmacological properties. In the present study, we demonstrate that the features of heterologously expressed rat TRPV2 closely resemble those of high-threshold heat-evoked currents in medium- and large-sized capsaicin-insensitive rat dorsal root ganglion (DRG) neurons. Both in TRPV2-expressing human embryonic kidney (HEK)293t cells and in DRGs, high-threshold heat-currents were sensitized by repeated activation and by the TRPV1-3 agonist, 2-aminoethoxydiphenyl borate (2-APB). In addition to a previously described block by ruthenium red, we identified the trivalent cations, lanthanum (La(3+)) and gadolinium (Gd(3+)) as potent blockers of TRPV2. Thus, we present a new pharmacological tool to distinguish between heat responses of TRPV2 and the closely related capsaicin-receptor, TRPV1, which is strongly sensitized by trivalent cations. We demonstrate that self-sensitization of heat-evoked currents through TRPV2 does not require extracellular calcium and that TRPV2 can be activated in cell-free membrane patches in the outside-out configuration. Taken together our results provide new evidence for a role of TRPV2 in mediating high-threshold heat responses in a subpopulation of mammalian sensory neurons.
机译：香草型TRP组（TRPV1-4）的热激活离子通道似乎对伤害性感觉神经元具有热敏感性。 TRPV2具有较高的激活阈值（> 52摄氏度），被提议作为哺乳动物感觉神经元中强烈有害热量的传感器。然而，尽管TRPV2在稀有髓鞘的初级传入细胞的不同群体中表达，但在各种神经元和非神经元组织中的广泛表达表明TRPV2的生理作用更为多样。就其作为热传感器的作用而言，TRPV2尚未在生物物理和药理特性方面得到全面表征。在本研究中，我们证明异源表达的大鼠TRPV2的特征与中大型辣椒素不敏感大鼠背根神经节（DRG）神经元中的高阈值热诱发电流的特征非常相似。无论是在表达TRPV2的人胚胎肾（HEK）293t细胞中，还是在DRG中，通过反复激活和TRPV1-3激动剂2-氨基乙氧基二苯基硼酸酯（2-APB）可以敏化高阈值的热流。除了先前描述的钌红阻滞作用外，我们还确定了三价阳离子镧（La（3+））和g（Gd（3+））是TRPV2的强力阻滞剂。因此，我们提出了一种新的药理学工具，以区分TRPV2和紧密相关的辣椒素受体TRPV1的热响应，而辣椒素受体TRPV1被三价阳离子强烈敏化。我们证明通过TRPV2的热诱发电流的自我敏化不需要细胞外钙，并且TRPV2可以在无细胞结构的膜片中由外而外激活。总之，我们的结果为TRPV2在介导哺乳动物感觉神经元亚群中的高阈值热反应中的作用提供了新的证据。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号