Neurotoxic activity of venom from the Australian Eastern mouse spider (Missulena bradleyi) involves modulation of sodium channel gating

Mouse spiders represent a potential cause of serious envenomation in humans. This study examined the activity of Missulena bradleyi venom in several in vitro preparations. Whilst female M. bradleyi venom at doses up to 0.05 μl ml−1 failed to alter twitch or resting tension in all preparations used, male venom (0.02 and 0.05 μl ml−1) produced potent effects on transmitter release in both smooth and skeletal neuromuscular preparations. In the mouse phrenic nerve diaphragm preparation, male M. bradleyi venom (0.02 μl ml−1) caused rapid fasciculations and an increase in indirectly evoked twitches. Male venom (0.02 and 0.05 μl ml−1) also caused a large contracture and rapid decrease in indirectly evoked twitches in the chick biventer cervicis muscle, however had no effect on responses to exogenous ACh (1 mM) or potassium chloride (40 mM). In the chick preparation, contractile responses to male M. bradleyi venom (0.05 μl ml−1) were attenuated by (+)-tubocurarine (100 μM) and by tetrodotoxin (TTX, 1 μM). Both actions of male M. bradleyi venom were blocked by Atrax robustus antivenom (2 units ml−1). In the unstimulated rat vas deferens, male venom (0.05 μl ml−1) caused contractions which were inhibited by a combination of prazosin (0.3 μM) and P2X-receptor desensitization (with α,β-methylene ATP 10 μM). In the rat stimulated vas deferens, male venom (0.05 μl ml−1) augmented indirectly evoked twitches. Male venom (0.1 μl ml−1) causes a slowing of inactivation of TTX-sensitive sodium currents in acutely dissociated rat dorsal root ganglion neurons. These results suggest that venom from male M. bradleyi contains a potent neurotoxin which facilitates neurotransmitter release by modifying TTX-sensitive sodium channel gating. This action is similar to that of the δ-atracotoxins from Australian funnel-web spiders. British Journal of Pharmacology (2000) 130, 1817–1824; doi:10.1038/sj.bjp.0703494