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

• DOI: 10.1038/s41467-020-16210-y
• Publication Date: 2020-05-08T10:03:04Z
• Authors: 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; Zhonghua Liu
• Keywords: NAV1; Knockout mouse; Spider toxin

The sodium channels Nav1.7, Nav1.8 and Nav1.9 are critical for pain perception in peripheral nociceptors. Loss of function Nav1.7 leads to congenital insensitivity humans. Here we show that the spider peptide toxin called HpTx1, first identified as an inhibitor Kv4.2, restores nociception knockout (Nav1.7-KO) mice by enhancing excitability dorsal root ganglion neurons. HpTx1 inhibits activates but does not affect Nav1.8. This produces wild-type (WT) Nav1.7-KO mice, attenuates Nav1.9-KO has no effect Nav1.8-KO mice. These data indicate HpTx1-induced hypersensitivity is mediated activation offers pharmacological insight into relationship three Nav signalling.