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_V1.5.