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

Abstract

Presynaptic- or β-neurotoxicity of secreted phospholipases A2 (sPLA2) 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.

Keywords

kačji strup;encimska aktivnost;snake venom;ammodytoxin;secreted phospholipase A2;anzymatic activity;cytochrome c oxidase;ß-neurotoxicity;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: IJS - Jožef Stefan Institute
UDC: 615:616-092:636.09
COBISS: 200247555 Link will open in a new window
ISSN: 1879-3150
Views: 65
Downloads: 10
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Other data

Secondary language: Slovenian
Secondary keywords: Snakes;Strupene kače;Encimska aktivnost;
Type (COBISS): Article
Pages: str. 1-6
Issue: ǂVol. ǂ247, [article no.] 107833
Chronology: 2024
DOI: 10.1016/j.toxicon.2024.107833
ID: 24512124