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Title: Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan krait (Bungarus candidus)
Authors: Nirthanan, S.
Charpantier, E.
Gopalakrishnakone, P.
Gwee, M.C.E.
Khoo, H.E.
Cheah, L.S.
Kini, R.M. 
Bertrand, D.
Keywords: Bungarus candidus
Neuromuscular junction
Nicotinic acetylcholine receptors
Postsynaptic neurotoxin
Three-finger toxin
Train-of-four fade
Issue Date: Jun-2003
Citation: Nirthanan, S., Charpantier, E., Gopalakrishnakone, P., Gwee, M.C.E., Khoo, H.E., Cheah, L.S., Kini, R.M., Bertrand, D. (2003-06). Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan krait (Bungarus candidus). British Journal of Pharmacology 139 (4) : 832-844. ScholarBank@NUS Repository.
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 (IC 50∼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- (IC 50∼2.2 nM) and a low-(IC 50∼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.
Source Title: British Journal of Pharmacology
ISSN: 00071188
Appears in Collections:Staff Publications

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