Comparative electrophysiological characterization of ammodytoxin A, a β-neurotoxin from the nose-horned viper venom, and its enzymatically inactive mutant

Žužek, Monika C. (author), Ivanušec, Adrijan (author), Herman, Julija (author), Šribar, Jernej (author), Leonardi, Adrijana (author), Frangež, Robert (author), Križaj, Igor (author)

Presynaptic- or β-neurotoxicity of secreted phospholipases A$_2$ (sPLA$_2$) is a complex process. For full expression of β-neurotoxicity, the enzymatic activity of the toxin is essential. However, it has been shown that not all toxic effects of a β-neurotoxin depend on its enzymatic activity, for example, the inhibition of mitochondrial cytochrome c oxidase. The main objective of this study was to verify whether it is possible to observe and study the phospholipase-independent actions of β-neurotoxins by a standard ex vivo twitch-tension experimental approach. To this end, we compared the effects of a potent snake venom β-neurotoxin, ammodytoxin A (AtxA), and its enzymatically inactive mutant AtxA(D49S) on muscle contraction of the mouse phrenic nerve-hemidiaphragm preparation. While AtxA significantly affected the amplitude of the indirectly evoked isometric muscle contraction, the resting tension of the neuromuscular (NM) preparation, the amplitude of the end-plate potential (EPP), the EPP half decay time and the resting membrane potential, AtxA(D49S) without enzymatic activity did not. From this, we can conclude that the effects of AtxA independent of enzymatic activity cannot be studied with classical electrophysiological measurements on the isolated NM preparation. Our results also suggest that the inhibition of cytochrome c oxidase activity by AtxA is not involved in the rapid NM blockade by this β-neurotoxin, but that its pathological consequences are rather long-term. Interestingly, in our experimental setup, AtxA upon direct stimulation reduced the amplitude of muscle contraction and induced contracture of the hemidiaphragm, effects that could be interpreted as myotoxic.

• Language: English
• Keywords: snake venom, ammodytoxin, secreted phospholipase A$_2$, enzymatic activity, cytochrome c oxidase, ß-neurotoxicity, snakes
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: VF - Veterinary Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 6 str.
• Numbering: Vol. 247, art. 107833
• PID: 20.500.12556/RUL-159212
• UDC: 615:616-092:636.09
• ISSN on article: 1879-3150
• DOI: 10.1016/j.toxicon.2024.107833
• COBISS.SI-ID: 200247555
• Publication date in RUL: 03.07.2024

Record is a part of a journal

• Title: Toxicon
• Shortened title: Toxicon
• Publisher: Elsevier, Brazilian Society of Toxinology, International Society on Toxinology, North American Society of Toxinology
• ISSN: 1879-3150
• COBISS.SI-ID: 183363843

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.

Secondary language

• Language: Slovenian
• Keywords: kačji strup, encimska aktivnost, strupene kače