Myotoxic activity of the crude venom and the principal neurotoxin, taipoxin, of the Australian taipan, Oxyuranus scutellatus

Abstract

1 The crude venom of the Australian taipan. Oxyuranus scutellatus and its principal neurotoxin, taipoxin, were injected into the anterolateral aspect of one hind limb of the rat. 2 The effects of the venom and toxin on the morphology and physiology on the underlying soleus muscles were examined. 3 Both the crude venom and the toxin caused necrosis and degeneration of the muscle. Damage to the peripheral muscle fibres could be seen at the light microscopic level as early as 3 h after injection of the toxic compounds. 4 The necrotic response was accompanied by an infiltration of phagocytic cells and an extensive oedema. The wet weight of the damaged muscles was almost doubled by 6 h. 5 In individual muscle fibres, necrosis was associated with the disruption of the plasma membrane and the disorganization of the myofibrils. The basal lamina of the muscle fibres was left intact. 6 Denervated mammalian muscles and innervated avian muscles were also destroyed by tiapoxin, but immature avian muscle growing in tissue culture was resistant. 7 Of the 3 subunits of taipoxin, only the basic alpha-taipoxin was itself myotoxic. However, its potency was enhanced by the presence of the acid gamma subunit. The role of the neutral beta-subunit is unclear. 8 The period of necrosis and degeneration lasted for approximately 48 h, after which the muscle fibres began to regenerate. Regeneration took place within the surviving basal lamina, with the formation of myotubes by three days, and small, immature muscle fibres by five days. Regeneration was virtually complete by 21 days.