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

• Type: Article in International Scientific Journal
• Date: 2017-09-01

Authors

José Bernardo Noronha-Matos (Author) ICBAS

Journal

Title: Toxicology and Applied Pharmacology

Vol. 334

Pages: 8-17

ISSN: 0041-008X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 5 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10