1. Spider venom-derived peptide induces hyperalgesia in Na v 1.7 knockout mice by activating Na v 1.9 channels.
- Author
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Zhou X, Ma T, Yang L, Peng S, Li L, Wang Z, Xiao Z, Zhang Q, Wang L, Huang Y, Chen M, Liang S, Zhang X, Liu JY, and Liu Z
- Subjects
- Amino Acid Sequence, Animals, Female, Ganglia, Spinal pathology, Humans, Hyperalgesia complications, Male, Mice, Knockout, NAV1.7 Voltage-Gated Sodium Channel chemistry, NAV1.8 Voltage-Gated Sodium Channel metabolism, NAV1.9 Voltage-Gated Sodium Channel chemistry, Neurons drug effects, Neurons pathology, Pain complications, Pain physiopathology, Rats, Hyperalgesia chemically induced, Hyperalgesia metabolism, Ion Channel Gating, NAV1.7 Voltage-Gated Sodium Channel metabolism, NAV1.9 Voltage-Gated Sodium Channel metabolism, Peptides adverse effects, Spider Venoms adverse effects
- Abstract
The sodium channels Na
v 1.7, Nav 1.8 and Nav 1.9 are critical for pain perception in peripheral nociceptors. Loss of function of Nav 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 Kv 4.2, restores nociception in Nav 1.7 knockout (Nav 1.7-KO) mice by enhancing the excitability of dorsal root ganglion neurons. HpTx1 inhibits Nav 1.7 and activates Nav 1.9 but does not affect Nav 1.8. This toxin produces pain in wild-type (WT) and Nav 1.7-KO mice, and attenuates nociception in Nav 1.9-KO mice, but has no effect in Nav 1.8-KO mice. These data indicate that HpTx1-induced hypersensitivity is mediated by Nav 1.9 activation and offers pharmacological insight into the relationship of the three Nav channels in pain signalling.- Published
- 2020
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