MrgprX1通过河豚毒素抗性钠通道介导神经元兴奋性和瘙痒。
MrgprX1 Mediates Neuronal Excitability and Itch Through Tetrodotoxin-Resistant Sodium Channels.
作者信息
Tseng Pang-Yen, Zheng Qin, Li Zhe, Dong Xinzhong
机构信息
The Solomon H. Snyder Department of Neuroscience and Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
出版信息
Itch (Phila). 2019 Jul-Sep;4(3). doi: 10.1097/itx.0000000000000028. Epub 2019 Aug 1.
In this study, we sought to elucidate the molecular mechanism underlying human Mas-related G protein-coupled receptor X1 (MrgprX1) mediated itch sensation. We found that activation of MrgprX1 by BAM8-22 triggered robust action potential discharges in dorsal root ganglion (DRG) neurons. This neuronal excitability is not mediated by Transient receptor potential (TRP) cation channels, M-type potassium channels, or chloride channels. Instead, activation of MrgprX1 lowers the activation threshold of TTX-resistant sodium channels and induces inward sodium currents. These MrgprX1-elicited action potential discharges can be blocked by Pertussis toxin (PTX) and a Gβγ inhibitor - Gallein. Behavioral results showed that Nav1.9 knockout but not Trpa1 knockout significantly reduced BAM8-22 evoked scratching behavior. Collectively, these data suggest that activation of MrgprX1 triggers itch sensation by increasing the activity of TTX-resistant voltage-gated sodium channels.
在本研究中，我们试图阐明人类Mas相关G蛋白偶联受体X1（MrgprX1）介导瘙痒感觉的分子机制。我们发现，BAM8-22激活MrgprX1会引发背根神经节（DRG）神经元强烈的动作电位发放。这种神经元兴奋性不是由瞬时受体电位（TRP）阳离子通道、M型钾通道或氯离子通道介导的。相反，MrgprX1的激活降低了耐河豚毒素钠通道的激活阈值并诱导内向钠电流。这些由MrgprX1引发的动作电位发放可被百日咳毒素（PTX）和一种Gβγ抑制剂——加林阻断。行为学结果表明，Nav1.9基因敲除而非Trpa1基因敲除显著降低了BAM8-22诱发的搔抓行为。总的来说，这些数据表明，MrgprX1的激活通过增加耐河豚毒素电压门控钠通道的活性来触发瘙痒感觉。
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