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We identified Tf2, the first β-scorpion toxin from the venom of the Brazilian scorpion  Tityus fasciolatus . Tf2 is identical to Tb2-II found in  Tityus bahiensis . We found that Tf2 selectively activates human (h)Na v 1.3, a neuronal voltage-gated sodium (Na v ) subtype implicated in epilepsy and nociception. Tf2 shifts hNa v 1.3 activation voltage to more negative values, thereby opening the channel at resting membrane potentials. Seven other tested mammalian Na v  channels (Na v 1.1-1.2; Na v 1.4-1.8) expressed in  Xenopus  oocytes are insensitive upon application of 1 μM Tf2. Therefore, the identification of Tf2 represents a unique addition to the repertoire of animal toxins that can be used to investigate Na v  channel function.

The Scorpion Toxin Tf2 from Tityus fasciolatus Promotes Nav1.3 Opening