Modification of sodium channel gating and kinetics by versutoxin from the 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 investigated under voltage-clamp conditions using the whole-cell patch-clamp technique. VTX had no effect on tetrodotoxin-resistant (TTX-R) sodium currents or potassium currents. In contrast VTX produced a dose-dependent slowing or removal of tetrodotoxin-sensitive (TTX-S) sodium current inactivation, a reduction in peak TTX-S sodium current but did not markedly slow tail current kinetics of TTX-S sodium currents. This steady-state sodium current was maintained during prolonged depolarizations at all test potentials and the reduction in sodium current amplitude produced by VTX had an apparent Ki of 37 nM. In the presence of 32 nM VTX the voltage dependence of steady-state sodium channel inactivation (h infinity) also showed a significant 7 mV shift in the voltage midpoint in the hyperpolarizing direction, with no change in the slope factor. In addition there was a steady-state or non-inactivating component present (14 +/- 2% of maximal sodium current) at prepulse potentials 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 selective actions of VTX on sodium channel gating and kinetics are similar to those of alpha-scorpion and sea anemone toxins.
Nicholson
G M
GM
Department of Biochemistry and Physiology, University of Technology, Sydney, Broadway, NSW, Australia.
Willow
M
M
Howden
M E
ME
Narahashi
T
T
D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D004347:Drug Interactions; D004351:Drug Resistance; D004594:Electrophysiology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D006706:Homeostasis; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology*; D013112:Spiders; D013779:Tetrodotoxin / Q000494:pharmacology
D002413:Cations, Divalent; D015221:Potassium Channels; D015222:Sodium Channels; D013111:Spider Venoms; C055477:versutoxin; D013779:Tetrodotoxin