2-aminoethoxydiphenyl borate activates and sensitizes the heat-gated ion channel TRPV3
2-aminoethoxydiphenyl borate activates and sensitizes the heat-gated ion channel TRPV3
复制标题
DOI：
10.1523/jneurosci.0934-04.2004
复制
发表时间：
2004-06-02
影响因子：
5.3
通讯作者：
Caterina, MJ
中科院分区：
文献类型：
--
作者：
Chung, MK;Lee, H;Caterina, MJ
哺乳动物瞬时受体电位（TRP）离子通道亚型中有六种是非选择性阳离子通道，可通过环境温度的升高或降低激活。其中五种可以通过非热刺激激活，如辣椒素[瞬时受体电位香草素1（TRPV 1）]或低渗透压（TRPV 2和TRPV 4）。尚未描述TRPV 3的非热刺激，TRPV 3是一种在皮肤角质形成细胞中显着表达的温门控离子通道。在这里，我们证明，2-氨基乙氧基二苯基硼酸酯（2-APB），一种用于抑制钙池操纵的钙通道和IP 3受体的化合物，产生强大的激活重组TRPV 3在人胚肾293细胞的EC 50为28 μ M。2-APB也敏感TRPV 3激活热，即使在阈下浓度。在来自TRPV 3表达细胞的由内而外的膜贴片中，2-APB增加了TRPV 3的开放概率。此外，尽管仅加热能够激活小部分原代小鼠角质形成细胞中的TRPV 3介导的电流，但2-APB激活大多数这些细胞中的热诱发的TRPV 3介导的电流。总之，这些发现将2-APB确定为TRPV 3的第一个已知化学活化剂，并增强了TRPV 3参与角质形成细胞检测热的概念。
Six of the mammalian transient receptor potential (TRP) ion channel subtypes are nonselective cation channels that can be activated by increases or decreases in ambient temperature. Five of them can alternatively be activated by nonthermal stimuli such as capsaicin [ transient receptor potential vanilloid 1 (TRPV1)] or hypo-osmolarity (TRPV2 and TRPV4). No nonthermal stimuli have yet been described for TRPV3, a warmth-gated ion channel expressed prominently in skin keratinocytes. Here, we demonstrate that 2-aminoethoxydiphenyl borate (2-APB), a compound used to inhibit store-operated Ca2+ channels and IP3 receptors, produces robust activation of recombinant TRPV3 in human embryonic kidney 293 cells with an EC50 of 28 muM. 2-APB also sensitizes TRPV3 to activation by heat, even at subthreshold concentrations. In inside-out membrane patches from TRPV3-expressing cells, 2-APB increases the open probability of TRPV3. Also, whereas heat alone is capable of activating TRPV3-mediated currents in only a small proportion of primary mouse keratinocytes, 2-APB activates heat-evoked, TRPV3-mediated currents in the majority of these cells. Together, these findings identify 2-APB as the first known chemical activator of TRPV3 and enhance the notion that TRPV3 participates in the detection of heat by keratinocytes.