Oxylepitoxin-1, a reversible neurotoxin from the venom of the inland taipan (Oxyuranus microlepidotus)

This study describes the characterization of oxylepitoxin-1 (MW 6789), the first postsynaptic neurotoxin isolated from the venom of the Inland taipan (Oxyuranus microlepidotus), which is the most venomous snake in the world. Oxylepitoxin-1, purified using successive steps of size-exclusion and reverse phase-high performance liquid chromatography, produced concentration-dependent (0.3–1.0 μM) inhibition of nerve-mediated (0.1 Hz, 0.2 ms, supramaximal V) twitches of the chick biventer cervicis nerve-muscle preparation. Taipan antivenom (5 units/ml) prevented the neurotoxic activity of whole venom (10 μg/ml), but had no significant effect on oxylepitoxin-1 (1 μM). The toxin-induced inhibition of nerve-mediated twitches was significantly reversed upon washing the tissue at 5 min intervals. Oxylepitoxin-1 (30–300 nM) displayed competitive antagonism at the skeletal muscle nicotinic receptor with a pA2 value of 7.16 ± 0.28 (i.e. approximately 10-fold more potent than tubocurarine). The venom had a high level of PLA2 activity (765 ± 73 μmol/min/mg) while oxylepitoxin-1 displayed no PLA2 activity. Partial N-terminal sequencing of oxylepitoxin-1 shows high sequence identity (i.e. 93%) to postsynaptic toxins isolated from the venom of the closely related coastal taipan (Oxyuranus scutellatus scutellatus).