Electrophysiological characterization of Tityus obscurus beta toxin 1 (To1) on Na+-channel isoforms

To1, previously named Tc49b, is a peptide neurotoxin isolated from venom of the scorpion Tityus obscurus that is responsible for lethal human poisoning cases in the Brazilian Amazonian region. Previously, To1 was shown to be lethal to mice and to change Na+ permeation in cerebellum granular neurons from rat brain. In addition, To1 did not affect Shaker B K+ channels. Based on sequence similarities, To1 was described as a beta-toxin. In the present work, To1 was purified from T. obscurus venom and submitted to an electrophysiological characterization in human and invertebrate Na-V channels. The analysis of the electrophysiological experiments reveal that To1 enhances the open probability at more negative potentials of human Na-V 1.3 and 1.6, of the insect channel BgNa(V)1 and of arachnid VdNa(V)1 channel. In addition, To1 reduces the peak of Na+ currents in some of the Na(V)s tested. These results support the classification of the To1 as a beta-toxin. A structure and functional comparison to other beta-toxins that share sequence similarity to To1 is also presented.