MODIFICATION OF SODIUM-CHANNEL GATING AND KINETICS BY VERSUTOXIN FROMTHE AUSTRALIAN FUNNEL-WEB SPIDER HADRONYCHE VERSUTA

The effects of a neurotoxin (versutoxin VTX), purified from the venom of the Australian Blue Mountains funnel-web spider Hadronyche versuta, on the ionic currents in rat dorsal root ganglion cells were investig ated under voltage-clamp conditions using the whole-cell patch-clamp t echnique. VTX had no effect on tetrodotoxin-resistant (TTX-R) sodium c urrents or potassium currents. In contrast VTX produced a dose-depende nt slowing or removal of tetrodotoxin-sensitive (TTX-S) sodium current inactivation, a reduction in peak TTX-S sodium current but did not ma rkedly slow tail current kinetics of TTX-S sodium currents. This stead y-state sodium current was maintained during prolonged depolarizations nt all test potentials and the reduction in sodium current amplitude produced by VTX had an apparent K-i of 37 nM. In the presence of 32 nM VTX the voltage dependence of steady-state sodium channel inactivatio n (h(i)nfinity) also showed a significant 7 mV shift in the voltage mi dpoint in the hyperpolarizing direction, with no change in the slope f actor. In addition there was a steady-state or non-inactivating compon ent present (14 +/- 2% of maximal sodium current) at prepulse potentia ls more depolarized than -40 mV, potentials which normally inactivate all TTX-S sodium channels. Finally, there was an observed increase in the rate of recovery from inactivation in the presence of VTX. These s elective actions of VTX on sodium channel gating and kinetics are simi lar to those of alpha-scorpion and sea anemone toxins.