Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider.
| Autor: | Finol-Urdaneta RK; Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia; rfinolu@uow.edu.au djadams@uow.edu.au p.alewood@imb.uq.edu.au.; Electrophysiology Facility for Cell Phenotyping and Drug Discovery, Wollongong, NSW 2522, Australia.; Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia., Ziegman R; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia., Dekan Z; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia., McArthur JR; Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.; Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia., Heitmann S; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia., Luna-Ramirez K; Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.; Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia., Tae HS; Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.; Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia., Mueller A; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia., Starobova H; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia., Chin YK; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.; Centre for Advanced Imaging, University of Queensland, St. Lucia, QLD 4072, Australia., Wingerd JS; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia., Undheim EAB; Centre for Advanced Imaging, University of Queensland, St. Lucia, QLD 4072, Australia.; Centre for Biodiversity Dynamics, Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway.; Centre for Ecology and Evolutionary Synthesis, Department of Bioscience, University of Oslo, 0316 Oslo, Norway., Cristofori-Armstrong B; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.; School of Biomedical Sciences, University of Queensland, St. Lucia, QLD 4072, Australia., Hill AP; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.; St Vincent's Clinical School, University of New South Wales Sydney, Darlinghurst, NSW 2010, Australia., Herzig V; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.; School of Science, Technology & Engineering and GeneCology Research Centre, University of the Sunshine Coast, Sippy Downs, QLD 4556, Australia., King GF; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.; Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, University of Queensland, St. Lucia, QLD 4072, Australia., Vetter I; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.; School of Pharmacy, University of Queensland, Woolloongabba, QLD 4102, Australia., Rash LD; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.; School of Biomedical Sciences, University of Queensland, St. Lucia, QLD 4072, Australia., Adams DJ; Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia; rfinolu@uow.edu.au djadams@uow.edu.au p.alewood@imb.uq.edu.au.; Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia., Alewood PF; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia; rfinolu@uow.edu.au djadams@uow.edu.au p.alewood@imb.uq.edu.au. |
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| Jazyk: | angličtina |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Feb 01; Vol. 119 (5). |
| DOI: | 10.1073/pnas.2110932119 |
| Abstrakt: | 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, δ/κ-theraphotoxin-Pm1a (δ/κ-TRTX-Pm1a), that elicited nocifensive behavior when injected into mice. In small dorsal root ganglion neurons, synthetic δ/κ-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 Na Competing Interests: The authors declare no competing interest. (Copyright © 2022 the Author(s). Published by PNAS.) |
| Databáze: | MEDLINE |
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