Abstract
Spider venoms are a complex mixture of peptides with a large number of neurotoxins targeting ion channels. Although thousands of peptide toxins have been identified from venoms of numerous species of spiders, many unknown species urgently need to be investigated. In this study, a novel sodium channel inhibitor, µ-TRTX-Hl1a, was identified from the venom of Haplopelma lividum. It contained eight cysteines and formed a conserved cysteine pattern of ICK motif. µ-TRTX-Hl1a inhibited the TTX-resistant (TTX-r) sodium channel current rather than the TTX-sensitive (TTX-s) sodium channel current. Meanwhile, µ-TRTX-Hl1a selectively inhibited NaV1.8 with an IC50 value of 2.19 μM. Intraperitoneal injection of µ-TRTX-Hl1a dose-dependently reduced inflammatory and neuropathic pain in rodent models of formalin-induced paw licking, tail-flicking, acetic acid-induced writhing, and hot plate test. It showed a better analgesic effect than morphine in inflammatory pain and equipotent effect to morphine in neuropathic pain. These findings demonstrate that µ-TRTX-Hl1a might be a valuable tool for physiology studies on NaV1.8 and a promising lead molecule for pain therapeutics.
Highlights
About 46,340 species of spiders live in the world, but only 1407 spider toxins have been identified from the venom of 97 species, whereas venom peptides from other species of spiders are still unknown [1]
A novel neurotoxin (μ-TRTX-Hl1a) with 39 amino acid residues was identified from the venom of the spider H. lividum [13]. μ-TRTX-Hl1a showed a selective inhibition on the sodium channel subtype NaV 1.8
An online BLAST search showed that μ-TRTX-Hl1a had considerable sequence similarity with other spider toxins such as JZTX-59 (U29-TRTX-Cj1a), toxic peptide C (U1-NETX-Csp1a) and Aps III (μ-CUTX-As1a)
Summary
Ping Meng 1,2,3,† , Honggang Huang 4,5,† , Gan Wang 6,† , Shilong Yang 1,2,3 , Qiuming Lu 1,2,3 , Jingze Liu 7, *, Ren Lai 1,2,3, * and Mingqiang Rong 1,2,3, *. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences &. United Laboratory of Natural Peptide of University of Science and Technology of China & Kunming. Sino-African Joint Research Center, Chinese Academy of Science, Wuhan 430074, Hubei, China. Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, Hebei, China.
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