Spider venom-derived peptide induces hyperalgesia in Na<sub>v</sub>1.7 knockout mice by activating Na<sub>v</sub>1.9 channels.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32385249.
- Also identified by DOI 10.1038/s41467-020-16210-y and PMC identifier 7210961.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The sodium channels Na<sub>v</sub>1.7, Na<sub>v</sub>1.8 and Na<sub>v</sub>1.9 are critical for pain perception in peripheral nociceptors. Loss of function of Na<sub>v</sub>1.7 leads to congenital insensitivity to pain in humans. Here we show that the spider peptide toxin called HpTx1, first identified as an inhibitor of K<sub>v</sub>4.2, restores nociception in Na<sub>v</sub>1.7 knockout (Na<sub>v</sub>1.7-KO) mice by enhancing the excitability of dorsal root ganglion neurons. HpTx1 inhibits Na<sub>v</sub>1.7 and activates Na<sub>v</sub>1.9 but does not affect Na<sub>v</sub>1.8. This toxin produces pain in wild-type (WT) and Na<sub>v</sub>1.7-KO mice, and attenuates nociception in Na<sub>v</sub>1.9-KO mice, but has no effect in Na<sub>v</sub>1.8-KO mice. These data indicate that HpTx1-induced hypersensitivity is mediated by Na<sub>v</sub>1.9 activation and offers pharmacological insight into the relationship of the three Na<sub>v</sub> channels in pain signalling.
Medical subject headings
- Hyperalgesia
- Ion Channel Gating
- NAV1.7 Voltage-Gated Sodium Channel
- NAV1.9 Voltage-Gated Sodium Channel
- Peptides
- Spider Venoms