Neuromuscular paralysis by the basic phospholipase A(2) subunit of crotoxin from Crotalus durissus terrificus snake venom needs its acid chaperone to concurrently inhibit acetylcholine release and produce muscle blockage

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017-09-01

Autores

José Bernardo Noronha-Matos (Autor) ICBAS

Revista

Título: Toxicology and Applied Pharmacology

Vol. 334

Páginas: 8-17

ISSN: 0041-008X

Editora: Elsevier

Indexação

ISI Web of Knowledge - 5 Citações

Scopus - 5 Citações

Outras Informações

ID Authenticus: P-00M-ZY1

DOI: 10.1016/j.taap.2017.08.021

Abstract (EN): Background and purpose: Crotoxin (CTX), a heterodimeric phospholipase A(2) (PLA(2)) neurotoxin from Crotalus durissus terrificus snake venom, promotes irreversible blockade of neuromuscular transmission. Indirect electrophysiological evidence suggests that CTX exerts a primary inhibitory action on transmitter exocytosis, yet contribution of a postsynaptic action of the toxin resulting from nicotinic receptor desensitization cannot be excluded. Here, we examined the blocking effect of CTX on nerve-evoked transmitter release measured directly using radioisotope neurochemistry and video microscopy with the FM4-64 fluorescent dye. Experimental approach: Experiments were conducted using mice phrenic-diaphragm preparations. Real-time fluorescence video microscopy and liquid scintillation spectrometry techniques were used to detect transmitter exocytosis and nerve-evoked [H-3] -acetylcholine ([H-3]ACh) release, respectively. Nerve-evoked myographic recordings were also carried out for comparison purposes. Key results: Both CTX (5 mu g/mL) and its basic PLA(2) subunit (CB, 20 mu g/mL) had biphasic effects on nerve-evoked transmitter exocytosis characterized by a transient initial facilitation followed by a sustained decay. CTX and CB reduced nerve-evoked [H-3]ACh release by 60% and 69%, respectively, but only the heterodimer, CTX, decreased the amplitude of nerve-evoked muscle twitches. Conclusion and implications: Data show that CTX exerts a presynaptic inhibitory action on ACh release that is highly dependent on its intrinsic PLA(2) activity. Given the high safety margin of the neuromuscular transmission, one may argue that the presynaptic block caused by the toxin is not enough to produce muscle paralysis unless a concurrent postsynaptic inhibitory action is also exerted by the CTX heterodimer.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10