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Article Dans Une Revue Toxicology Letters Année : 2017

Natural polymeric 3-alkylpyridinium salt affects vertebrate skeletal muscle contractility by preferentially blocking neuromuscular transmission

Résumé

The effects of natural polymeric alkylpyridinium salt (nPoly-3-APS), a potent acetylcholinesterase inhibitor isolated from the marine sponge Reniera sarai, were studied on isolated mouse phrenic nerve-hemidiaphragm muscle preparations using electrophysiological approaches. nPoly-3-APS inhibited nerve-evoked isometric muscle twitch and tetanic contraction in a concentration-dependent manner (IC50=29.4μM and 18.5μM, respectively) and produced a 30-44% decrease of directly muscle-elicited twitch and tetanus amplitudes at 54.4μM. Additionally, nPoly-3-APS (9.1-27.2μM) markedly decreased the amplitude of miniature endplate potentials, while their frequency was only affected at the highest concentration used. Endplate potentials were also inhibited by nPoly-3-APS in a concentration-dependent manner (IC50=20.1μM), without significant change in the resting membrane potential of muscle fibers (up to 54.4μM). In conclusion, our results show, for the first time, that nPoly-3-APS preferentially blocks the neuromuscular transmission, in vitro, by a non-depolarizing mechanism. This strongly suggests that the in vivo toxicity of nPoly-3-APS mainly occurs through an antagonist action of the compound on nicotinic acetylcholine receptors of skeletal muscles.
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Dates et versions

hal-01661797 , version 1 (21-05-2020)

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Monika Cecilija Žužek, Marjana Grandič, Evelyne Benoit, Robert Frangež. Natural polymeric 3-alkylpyridinium salt affects vertebrate skeletal muscle contractility by preferentially blocking neuromuscular transmission. Toxicology Letters, 2017, 281, pp.95-101. ⟨10.1016/j.toxlet.2017.09.007⟩. ⟨hal-01661797⟩
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