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

Wayne C. Hodgson, Cháriston André Dal Belo, E.G. Rowan

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.
LanguageEnglish
Pages1229-36
Number of pages1193
JournalNeuropharmacology
Volume52
Issue number5
DOIs
Publication statusPublished - 2007

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Venoms
Neurotoxins
Diaphragm
paradoxin
Phrenic Nerve
Snakes
Carbachol
Acetylcholine
Fibroblasts
Pharmacology
Muscles
Temperature

Keywords

  • neurotoxin
  • snake
  • nenom
  • presynaptic
  • neuromuscular transmission
  • pharmacology

Cite this

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The neuromuscular activity of paradoxin: a presynaptic neurotoxin from the venom of the inland taipan (Oxyuranus microlepidotus). / Hodgson, Wayne C.; Dal Belo, Cháriston André; Rowan, E.G.

In: Neuropharmacology, Vol. 52, No. 5, 2007, p. 1229-36.

Research output: Contribution to journalArticle

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T1 - The neuromuscular activity of paradoxin: a presynaptic neurotoxin from the venom of the inland taipan (Oxyuranus microlepidotus)

AU - Hodgson, Wayne C.

AU - Dal Belo, Cháriston André

AU - Rowan, E.G.

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PY - 2007

Y1 - 2007

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AB - 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.

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