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The neuromuscular activity of paradoxin: a presynaptic neurotoxin from the venom of the inland taipan (Oxyuranus microlepidotus)

Hodgson, Wayne C. and Dal Belo, Cháriston André and Rowan, E.G. (2007) The neuromuscular activity of paradoxin: a presynaptic neurotoxin from the venom of the inland taipan (Oxyuranus microlepidotus). Neuropharmacology, 52 (5). pp. 1229-36. ISSN 0028-3908

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Abstract

The inland taipan is the world's most venomous snake. However, little is known about the neuromuscular activity of the venom or paradoxin (PDX), a presynaptic neurotoxin from the venom. Venom (10microg/ml) and PDX (65nM) abolished indirect twitches of the chick biventer cervicis and mouse phrenic nerve diaphragm preparations. The time to 90% inhibition by PDX was significantly increased by replacing Ca(2+) (2.5mM) in the physiological solution with Sr(2+) (10mM). In the biventer cervicis muscle, venom (10microg/ml), but not PDX (65nM), significantly inhibited responses to ACh (1mM) and carbachol (20microM), but not KCl (40mM). In the mouse diaphragm (low Ca(2+); room temperature), the inhibitory effect of PDX (6.5nM) was delayed and a transient increase (746+/-64%; n=5) of contractions observed. In intracellular recording experiments using the mouse hemidiaphragm, PDX (6.5-65nM) significantly increased quantal content and miniature endplate potential frequency prior to blocking evoked release of acetylcholine. In extracellular recording experiments using the mouse triangularis sterni, PDX (2.2-65nM) significantly inhibited the voltage-dependent K(+), but not Na(+), waveform. In patch clamp experiments using B82 mouse fibroblasts stably transfected with rKv 1.2, PDX (22nM; n=3) had no significant effect on currents evoked by 10mV step depolarisations from -60 to +20mV. PDX exhibits all the pharmacology associated with beta-neurotoxins, and appears to be one of the most potent, if not the most potent beta-neurotoxin yet discovered.

Item type: Article
ID code: 18482
Notes: PMID: 17313963
Keywords: neurotoxin, snake, nenom, presynaptic, neuromuscular transmission, pharmacology, Physiology, Therapeutics. Pharmacology, Cellular and Molecular Neuroscience, Pharmacology
Subjects: Science > Physiology
Medicine > Therapeutics. Pharmacology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Dr EG Rowan
    Date Deposited: 31 Mar 2010 12:51
    Last modified: 05 Sep 2014 01:35
    URI: http://strathprints.strath.ac.uk/id/eprint/18482

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