Identification of presynaptic neurotoxin complexes in the venoms of three Australian copperheads (Austrelaps spp.) and the efficacy of tiger snake antivenom to prevent or reverse neurotoxicity.

Abstract

The venom of the Australian lowlands copperhead, Austrelaps superbus, produces significant and potentially lethal neurotoxic paralysis in cases of clinical envenomation. However, little is known about the neurotoxic components within this venom or venoms from the related alpine copperhead (Austrelaps ramsayi) or pygmy copperhead (Austrelaps labialis). Using the isolated chick biventer cervicis nerve-muscle preparation, all Austrelaps venoms were found to exhibit potent and rapid inhibition of nerve-evoked twitch contractions and block of contractures to nicotinic agonists, consistent with postsynaptic neurotoxic activity. Following separation by size-exclusion liquid chromatography under non-denaturing conditions, all Austrelaps venoms were found to also contain a high molecular mass fraction with only weak phospholipase A(2) (PLA(2)) activity that caused a slow inhibition of twitch contractions, without inhibiting contractures to nicotinic agonists. These actions are consistent with the presence of additional snake presynaptic PLA(2) neurotoxin (SPAN) complexes in all three Austrelaps venoms. However, there was no evidence of direct muscle damage produced by any Austrelaps venom or SPAN complex. Monovalent tiger snake antivenom was effective in neutralising the neurotoxicity of both whole venom and the SPAN complex. However antivenom was unable to effectively reverse whole venom neurotoxicity, or prejunctional SPAN neurotoxicity, once established. Given the strong neurotoxicity of all Austrelaps venoms, particularly A. ramsayi and A. labialis, effective bites from these copperhead species should be considered potentially lethal. Furthermore, clinicians need to be aware of possible irreversible presynaptic neurotoxicity following envenomation from all copperhead species and that early antivenom intervention is important in preventing further development of toxicity.