title: The neuromuscular activity of paradoxin: a presynaptic neurotoxin from the venom of the inland taipan (Oxyuranus microlepidotus).
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.
authors.affiliation: Monash Venom Group, Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia. wayne.hodgson@med.monash.edu.au
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Hodgson
authors.forename: Cháriston André
authors.initials: CA
authors.lastname: Dal Belo
authors.forename: Edward G
authors.initials: EG
authors.lastname: Rowan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D003964:Diaphragm / Q000187:drug effects; D004546:Elapid Venoms / Q000633:toxicity*; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity*; D018408:Patch-Clamp Techniques; D010741:Phospholipases A / Q000378:metabolism; D010791:Phrenic Nerve / Q000187:drug effects; D017661:Receptors, Presynaptic / Q000187:drug effects*; D012911:Snakes / Q000502:physiology*; D013324:Strontium
chemical_list: D004546:Elapid Venoms; D009498:Neurotoxins; D017661:Receptors, Presynaptic; C521070:paradoxin; D010741:Phospholipases A; D013324:Strontium