LmNaTx15, a novel scorpion toxin, enhances the activity of Nav channels and induces pain in mice

Minzhi Chen; Minjuan Lu; Xujun Feng; Meijing Wu; Xiaoqing Luo; Ruiqi Xiang; Ren Luo; Hang Wu; Zhonghua Liu; Meichi Wang; Xi Zhou

doi:10.1016/j.toxicon.2023.107331

LmNaTx15, a novel scorpion toxin, enhances the activity of Nav channels and induces pain in mice

Toxicon. 2023 Dec:236:107331. doi: 10.1016/j.toxicon.2023.107331. Epub 2023 Nov 1.

Authors

Minzhi Chen¹, Minjuan Lu¹, Xujun Feng¹, Meijing Wu¹, Xiaoqing Luo¹, Ruiqi Xiang¹, Ren Luo¹, Hang Wu¹, Zhonghua Liu¹, Meichi Wang², Xi Zhou³

Affiliations

¹ The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, China; Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, 410081, China; Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha, 410081, Hunan, China.
² The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, China; Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, 410081, China; Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha, 410081, Hunan, China. Electronic address: wangmeichi@hunnu.edu.cn.
³ The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, China; Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, 410081, China; Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha, 410081, Hunan, China. Electronic address: xizh@hunnu.edu.cn.

PMID: 37918718
DOI: 10.1016/j.toxicon.2023.107331

Abstract

Polypeptide toxins are major bioactive components found in venomous animals. Many polypeptide toxins can specifically act on targets, such as ion channels and voltage-gated sodium (Nav) channels, in the nervous, muscle, and cardiovascular systems of the recipient to increase defense and predation efficiency. In this study, a novel polypeptide toxin, LmNaTx15, was isolated from the venom of the scorpion Lychas mucronatus, and its activity was analyzed. LmNaTx15 slowed the fast inactivation of Nav1.2, Nav1.3, Nav1.4, Nav1.5, and Nav1.7 and inhibited the peak current of Nav1.5, but it did not affect Nav1.8. In addition, LmNaTx15 altered the voltage-dependent activation and inactivation of these Nav channel subtypes. Furthermore, like site 3 neurotoxins, LmNaTx15 induced pain in mice. These results show a novel scorpion toxin with a modulatory effect on specific Nav channel subtypes and pain induction in mice. Therefore, LmNaTx15 may be a key bioactive component for scorpion defense and predation. Besides, this study provides a basis for analyzing structure-function relationships of the scorpion toxins affecting Nav channel activity.

Keywords: Inactivation; Pain; Scorpion toxins; Sodium channels.

MeSH terms

Animals
Mice
Neurotoxins
Pain / chemically induced
Pain / drug therapy
Peptides
Scorpion Venoms* / toxicity

Substances

Scorpion Venoms
Neurotoxins
Peptides