Subtype Specificity of β-Toxin Tf1a from Tityus fasciolatus in Voltage Gated Sodium Channels

Scorpion venoms are a complex mixture of components. Among them the most important are peptides, which presents the capacity to interact and modulate several ion channel subtypes, including voltage-gated sodium channels (Na(V)). Screening the activity of scorpion toxins on different subtypes of Na(V) reveals the scope of modulatory activity and, in most cases, low channel selectivity. Until now there are approximately 60 scorpion toxins experimentally assayed on Na(V) channels. However, the molecular bases of interaction between scorpion toxins and Na(V) channels are not fully elucidated. The activity description of new scorpion toxins is crucial to enhance the predictive strength of the structural–function correlations of these Na(V) modulatory molecules. In the present work a new scorpion toxin (Tf1a) was purified from Tityus fasciolatus venom by RP-HPLC, and characterized using electrophysiological experiments on different types of voltage-gated sodium channels. Tf1a was able to modify the normal function of Na(V) tested, showing to be a typical β-NaScTx. Tf1a also demonstrated an unusual capability to alter the kinetics of Na(V)1.5.