Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider-Reference-Cited by-同舟云学术

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

Published:2022-01-24 Issue:5 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Finol-Urdaneta Rocio K.¹²³^ORCID,Ziegman Rebekah⁴^ORCID,Dekan Zoltan⁴^ORCID,McArthur Jeffrey R.¹³^ORCID,Heitmann Stewart⁵^ORCID,Luna-Ramirez Karen¹³,Tae Han-Shen¹³^ORCID,Mueller Alexander⁴^ORCID,Starobova Hana⁴^ORCID,Chin Yanni K.-Y.⁴⁶^ORCID,Wingerd Joshua S.⁴,Undheim Eivind A. B.⁶⁷⁸,Cristofori-Armstrong Ben⁴⁹^ORCID,Hill Adam P.⁵¹⁰^ORCID,Herzig Volker⁴¹¹^ORCID,King Glenn F.⁴¹²^ORCID,Vetter Irina⁴¹³^ORCID,Rash Lachlan D.⁴⁹^ORCID,Adams David J.¹³^ORCID,Alewood Paul F.⁴^ORCID

Affiliation:

1. Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia

2. Electrophysiology Facility for Cell Phenotyping and Drug Discovery, Wollongong, NSW 2522, Australia

3. Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia

4. Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia

5. Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia

6. Centre for Advanced Imaging, University of Queensland, St. Lucia, QLD 4072, Australia

7. Centre for Biodiversity Dynamics, Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway

8. Centre for Ecology and Evolutionary Synthesis, Department of Bioscience, University of Oslo, 0316 Oslo, Norway

9. School of Biomedical Sciences, University of Queensland, St. Lucia, QLD 4072, Australia

10. St Vincent's Clinical School, University of New South Wales Sydney, Darlinghurst, NSW 2010, Australia

11. School of Science, Technology & Engineering and GeneCology Research Centre, University of the Sunshine Coast, Sippy Downs, QLD 4556, Australia

12. Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, University of Queensland, St. Lucia, QLD 4072, Australia

13. School of Pharmacy, University of Queensland, Woolloongabba, QLD 4102, Australia

Abstract

Significance Pain development and discomfort are universal features of spider envenomation, yet severe pain arising from bites by Old World spiders is poorly understood. Molecular analyses of the venom of the King Baboon spider revealed abundant expression of the inhibitory cystine knot peptide Pm1a. Synthetic Pm1a induces pain in mice while simultaneously enhancing proexcitatory sodium currents and decreasing inhibitory potassium currents. These concomitant effects promote hyperexcitability in pain-sensing neurons that can be reversed by pharmacological inhibition of voltage-gated sodium channels. The coordinated modulation of excitatory and inhibitory ion channels involved in pain propagation may represent an economical and effective defense strategy in pain-inducing defensive venoms.

Funder

Department of Health | National Health and Medical Research Council

Australian Research Council

Rebecca L. Cooper Medical Research Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2110932119

Reference65 articles.

1. Venom components from Citharischius crawshayi spider (Family Theraphosidae): exploring transcriptome, venomics, and function