Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan krait (Bungarus candidus).

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Title Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan krait (Bungarus candidus).
Author Nirthanan, S. Niru; Charpantier, E; Gopalakrishnakone, P; Gwee, M C E; Khoo, H E; Cheah, L S; Kini, R M; Bertrand, D
Journal Name British Journal of Pharmacology
Year Published 2003
Place of publication United States
Publisher Nature Publishing Group
Abstract 1 Candoxin (MW 7334.6), a novel toxin isolated from the venom of the Malayan krait Bungarus candidus, belongs to the poorly characterized subfamily of nonconventional three-finger toxins present in Elapid venoms. The current study details the pharmacological effects of candoxin at the neuromuscular junction. 2 Candoxin produces a novel pattern of neuromuscular blockade in isolated nerve-muscle preparations and the tibialis anterior muscle of anaesthetized rats. In contrast to the virtually irreversible postsynaptic neuromuscular blockade produced by curaremimetic α-neurotoxins, the neuromuscular blockade produced by candoxin was rapidly and completely reversed by washing or by the addition of the anticholinesterase neostigmine. 3 Candoxin also produced significant train-of-four fade during the onset of and recovery from neuromuscular blockade, both, in vitro and in vivo. The fade phenomenon has been attributed to a blockade of putative presynaptic nicotinic acetylcholine receptors (nAChRs) that mediate a positive feedback mechanism and maintain adequate transmitter release during rapid repetitive stimulation. In this respect, candoxin closely resembles the neuromuscular blocking effects of d-tubocurarine, and differs markedly from curaremimetic α-neurotoxins that produce little or no fade. 4 Electrophysiological experiments confirmed that candoxin produced a readily reversible blockade (IC50∼10 nM) of oocyte-expressed muscle (αβγδ) nAChRs. Like α-conotoxin MI, well known for its preferential binding to the α/δ interface of the muscle (αβγδ) nAChR, candoxin also demonstrated a biphasic concentration - response inhibition curve with a high- (IC50∼2.2 nM) and a low-(IC50∼98 nM) affinity component, suggesting that it may exhibit differential affinities for the two binding sites on the muscle (αβγδ) receptor. In contrast, curaremimetic α-neurotoxins have been reported to antagonize both binding sites with equal affinity.
Peer Reviewed Yes
Published Yes
Publisher URI http://www.brjpharmacol.org/view/0/index.html
Alternative URI http://dx.doi.org/10.1038/sj.bjp.0705299
Volume 139
Issue Number 4
Page from 832
Page to 844
ISSN 0007-1188
Date Accessioned 2009-07-09
Date Available 2009-12-18T06:32:39Z
Language en_AU
Research Centre Griffith Health Institute
Faculty Griffith Health Faculty
Subject Basic Pharmacology
URI http://hdl.handle.net/10072/27757
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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