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

1 Mouse spiders represent a potential cause of serious envenomation in huma ns. This study examined the activity of Missulena bradleyi venom in several in? vitro preparations. Whilst female M. bradleyi venom at doses up to 0.0 5 mu l ml(-1) failed to alter twitch or resting tension in all preparations used, male venom (0.02 and 0.05 mu l ml(-1)) produced potent effects on tr ansmitter release in both smooth and skeletal neuromuscular preparations. 2 In the mouse phrenic nerve diaphragm preparation, male M, bradleyi venom (0.02 mu l ml(-1)) caused rapid fasciculations and an increase in indirectl y evoked twitches. 3 Male venom (0.02 and 0.05 mu l ml(-1)) also caused a large contracture an d rapid decrease in indirectly evoked twitches in the chick biventer cervic is muscle, however had no effect on responses to exogenous ACh (1 mM) or po tassium chloride (40 mM). In the chick preparation, contractile responses t o male M. bradleyi venom (0.05 mu l ml(-1)) were attenuated by (+)-tubocura rine (100 mu M) and by tetrodotoxin (TTX, 1 mu M). Both actions of male M. bradleyi venom were blocked by Atrax robustus antivenom (2 units ml(-1)). 4 In the unstimulated rat vas deferens, male venom (0.05 mu l ml(-1)) cause d contractions which were inhibited by a combination of prazosin (0.3 mu M) and P-2X-receptor desensitization (with alpha,beta-methylene ATP 10 mu M). In the rat stimulated vas deferens, male venom (0.05 mu l ml(-1)) augmente d indirectly evoked twitches. 5 Male venom (0.1 mu l ml(-1)) causes a slowing of inactivation of TTX-sens itive sodium currents in acutely dissociated rat dorsal root ganglion neuro ns. 6 These results suggest that venom from male M. bradleyi contains a potent neurotoxin which facilitates neurotransmitter release by modifying TTX-sens itive sodium channel gating. This action is similar to that of the delta-at racotoxins from Australian funnel-web spiders.