The effect ofTityus serrulatus scorpion toxin γ on Na channels in neuroblastoma cells

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Abstract
The effect of highly purified toxin γ from the venom of the scorpionTityus serrulatus (TiTxγ) on nerve membrane ionic channels have been investigated using the suction electrodes voltage clamp technique on neuroblastoma cells. The amplitude of the normally voltage-dependent Na current is reversible reduced by approximately 50% after 15–105 nM TiTxγ, whereas even the highest toxin concentrations have no significant effect on the outward K current in the presence of tetrodotoxin. TiTxγ causes a transient inward current to appear at membrane potentials between −70 and −40 mV, a potential region in which no significant inward current is observed in control experiments. Tetrodotoxin (300 nM) rapidly blocks both the TiTxγ-induced inward current and the remaining normally voltagedependent Na current. The binding of radiolabelled TiTxγ to the Na channels in the neuroblastoma cell membrane is prevented by native TiTxγ with aK 0.5=0.75 nM. Both activation and inactivation of the TiTxγ-induced Na current are shifted 30–40 mV towards more negative potential values as compared to normally voltage-dependent Na current. The TiTxγ-induced Na current exhibits sigmoidal activation kinetics and relatively slow, exponential inactivation kinetics. The local anesthetic procaine at an external concentration of 1 mM blocks more effectively the remaining normally voltage-dependent Na current than the TiTxγ-induced Na current. Both Na current components are equally blocked by 1 mM of the local anesthetic propoxycaine. The relation between the effects of TiTxγ on Na+ channels and those of other known neurotoxins specific of this channel is discussed. It is concluded that the characteristic effects of TiTxγ differ from those of all other known toxins including other scorpion toxins that bind to the same site on the Na channel.

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