Spider venom-derived peptide induces hyperalgesia in Nav1.7 knockout mice by activating Nav1.9 channels

Xi Zhou, Tingbin Ma, Luyao Yang, Shuijiao Peng, Lulu Li, Zhouquan Wang, Zhen Xiao, Qingfeng Zhang, Li Wang, Yazhou Huang, Minzhi Chen, Songping Liang, Xianwei Zhang, Jing Yu Liu () and Zhonghua Liu ()
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Xi Zhou: Hunan Normal University
Tingbin Ma: Huazhong University of Science and Technology (HUST)
Luyao Yang: Huazhong University of Science and Technology (HUST)
Shuijiao Peng: Hunan Normal University
Lulu Li: Huazhong University of Science and Technology (HUST)
Zhouquan Wang: Hunan Normal University
Zhen Xiao: Hunan Normal University
Qingfeng Zhang: Hunan Normal University
Li Wang: Hunan Normal University
Yazhou Huang: Hunan Normal University
Minzhi Chen: Hunan Normal University
Songping Liang: Hunan Normal University
Xianwei Zhang: Tongji Hospital of HUST
Jing Yu Liu: Huazhong University of Science and Technology (HUST)
Zhonghua Liu: Hunan Normal University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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 Nav channels in pain signalling.

Date: 2020
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DOI: 10.1038/s41467-020-16210-y

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