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Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider

Journal Article


Abstract


  • The King Baboon spider, Pelinobius muticus, is a burrowing African tarantula. Its impressive size and appealing coloration are tempered by reports describing severe localized pain, swelling, itchiness, and muscle cramping after accidental envenomation. Hyperalgesia is the most prominent symptom after bites from P. muticus, but the molecular basis by which the venom induces pain is unknown. Proteotranscriptomic analysis of P. muticus venom uncovered a cysteine-rich peptide, ��/��-theraphotoxin-Pm1a (��/��-TRTX-Pm1a), that elicited nocifensive behavior when injected into mice. In small dorsal root ganglion neurons, synthetic ��/��-TRTX-Pm1a (sPm1a) induced hyperexcitability by enhancing tetrodotoxin-resistant sodium currents, impairing repolarization and lowering the threshold of action potential firing, consistent with the severe pain associated with envenomation. The molecular mechanism of nociceptor sensitization by sPm1a involves multimodal actions over several ion channel targets, including NaV1.8, KV2.1, and tetrodotoxin-sensitive NaV channels. The promiscuous targeting of peptides like ��/��-TRTX-Pm1a may be an evolutionary adaptation in pain-inducing defensive venoms.

Publication Date


  • 2022

Citation


  • Finol-Urdaneta, R. K., Ziegman, R., Dekan, Z., McArthur, J. R., Heitmann, S., Luna-Ramirez, K., . . . Alewood, P. F. (2022). Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider. Proceedings of the National Academy of Sciences of the United States of America, 119(5). doi:10.1073/pnas.2110932119

Scopus Eid


  • 2-s2.0-85123423278

Volume


  • 119

Issue


  • 5

Place Of Publication


Abstract


  • The King Baboon spider, Pelinobius muticus, is a burrowing African tarantula. Its impressive size and appealing coloration are tempered by reports describing severe localized pain, swelling, itchiness, and muscle cramping after accidental envenomation. Hyperalgesia is the most prominent symptom after bites from P. muticus, but the molecular basis by which the venom induces pain is unknown. Proteotranscriptomic analysis of P. muticus venom uncovered a cysteine-rich peptide, ��/��-theraphotoxin-Pm1a (��/��-TRTX-Pm1a), that elicited nocifensive behavior when injected into mice. In small dorsal root ganglion neurons, synthetic ��/��-TRTX-Pm1a (sPm1a) induced hyperexcitability by enhancing tetrodotoxin-resistant sodium currents, impairing repolarization and lowering the threshold of action potential firing, consistent with the severe pain associated with envenomation. The molecular mechanism of nociceptor sensitization by sPm1a involves multimodal actions over several ion channel targets, including NaV1.8, KV2.1, and tetrodotoxin-sensitive NaV channels. The promiscuous targeting of peptides like ��/��-TRTX-Pm1a may be an evolutionary adaptation in pain-inducing defensive venoms.

Publication Date


  • 2022

Citation


  • Finol-Urdaneta, R. K., Ziegman, R., Dekan, Z., McArthur, J. R., Heitmann, S., Luna-Ramirez, K., . . . Alewood, P. F. (2022). Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider. Proceedings of the National Academy of Sciences of the United States of America, 119(5). doi:10.1073/pnas.2110932119

Scopus Eid


  • 2-s2.0-85123423278

Volume


  • 119

Issue


  • 5

Place Of Publication