Australian funnel-web spider toxin, versutoxin, enhances spontaneous synaptic activity in single brain neurons in...

Neurotoxins isolated from the venoms of Australian funnel-web spiders increase spontaneous action potential activity in a variety of excitable cells. In the present study intracellular recordings were made with microelectrodes (30-60 M omega, 2 M KCl) from locus coeruleus, mesencephalic nucleus of the trigeminal nerve and laterodorsal tegmental neurons in brain slices. Versutoxin, a polypeptide toxin isolated from the venom of Hadronyche versutus produced a profound increase in spontaneous synaptic activity impinging on neurons, which did not fully recover for up to 3 h after washout. The threshold concentration was 1.5 nM in locus coeruleus neurons, with increasing concentrations (up to 50 nM) producing larger effects. A modest increase in synaptic activity was observed in mesencephalic nucleus of the trigeminal nerve neurons during superfusion with 50 nM versutoxin. The increase in spontaneous synaptic activity was reversed by agents which block synaptic potentials impinging on locus coeruleus neurons, i.e., tetrodotoxin (100 nM), Co2+ (3 mM) or the combination of 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and bicuculline (30 microM). Threshold, peak amplitude, maximum rate of rise, duration, amplitude of afterhyperpolarisations and interspike intervals of action potentials in each type of neuron were unaffected by versutoxin. Voltage-current relationships were also unaffected. Calcium-dependent action potentials evoked in locus coeruleus neurons in the presence of tetrodotoxin were unaffected by versutoxin, as were depolarisations produced by exogenously applied glutamate. These results suggest that versutoxin increases spontaneous synaptic activity, but has no effect on the membrane properties of the soma of several types of rat brain neurons.