Spider venom-derived peptide induces hyperalgesia in Nav1.7 knockout mice by activating Nav1.9 channels
Spider venom-derived peptide induces hyperalgesia in Nav1.7 knockout mice by activating Nav1.9 channels
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蜘蛛毒肽通过激活 Na(v)1.9 通道诱导 Na(v)1.7 敲除小鼠痛觉过敏
DOI：
10.1038/s41467-020-16210-y
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发表时间：
2020
影响因子：
16.6
通讯作者：
Liu Zhonghua
中科院分区：
文献类型：
--
作者：
Zhou Xi;Ma Tingbin;Yang Luyao;Peng Shuijiao;Li Lulu;Wang Zhouquan;Xiao Zhen;Zhang Qingfeng;Wang Li;Huang Yazhou;Chen Minzhi;Liang Songping;Zhang Xianwei;Liu Jing Yu;Liu Zhonghua
钠通道Nav1.7、Nav1.8和Nav1.9对外周伤害性感受器的痛觉起关键作用。在人类中，Nav1.7功能的丧失会导致先天对疼痛不敏感。在这里，我们证明了名为HpTx1的蜘蛛肽毒素，最初被确定为Kv4.2的抑制物，通过增强背根神经节神经元的兴奋性来恢复Nav1.7基因敲除(Nav1.7-KO)小鼠的伤害性。HpTx1抑制Nav1.7并激活Nav1.9，但不影响Nav1.8。这种毒素对野生型(WT)和Nav1.7-KO小鼠产生疼痛，并减弱Nav1.9-KO小鼠的伤害性，但对Nav1.8-KO小鼠没有影响。这些数据表明，HpTx1诱导的超敏反应是由Nav1.9激活介导的，并为了解这三个Nav通道在疼痛信号中的关系提供了药理学见解。
The sodium channels Nav1.7, Nav1.8 and Nav1.9 are critical for pain perception in peripheral nociceptors. Loss of function of Nav1.7 leads to congenital insensitivity to pain in humans. Here we show that the spider peptide toxin called HpTx1, first identified as an inhibitor of Kv4.2, restores nociception in Nav1.7 knockout (Nav1.7-KO) mice by enhancing the excitability of dorsal root ganglion neurons. HpTx1 inhibits Nav1.7 and activates Nav1.9 but does not affect Nav1.8. This toxin produces pain in wild-type (WT) and Nav1.7-KO mice, and attenuates nociception in Nav1.9-KO mice, but has no effect in Nav1.8-KO mice. These data indicate that HpTx1-induced hypersensitivity is mediated by Nav1.9 activation and offers pharmacological insight into the relationship of the three Navchannels in pain signalling.