Electrophysiological characterization of the peptide Tf3 isolated from the venom of Tityus fasciolatus on voltage-gated sodium channels Naᵥ1.2, Naᵥ1.6, and Naᵥ1.7

The study of scorpion venom has unveiled a rich source of bioactive peptides with significant therapeutic potential, particularly in modulating ion channels. Among these peptides are those containing disulfide bridges in their structure, a feature that endows them with the capacity to modulate voltage-gated channels. These neurotoxins, as they are known, are classified into two distinct groups based on their structure and mode of action on these channels: α-toxins and β-toxins.This study aimed to characterize the electrophysiological properties of Tf3, an α-toxin extracted from the venom of the cerrado's scorpion species Tityus fasciolatus, focusing on its interaction with three mammalian isoforms of voltage-gated sodium channels (Naᵥ): Naᵥ1.2, Naᵥ1.6, and Naᵥ1.7. Using patch-clamp techniques on cells expressing these channels, three distinct protocols were performed under control conditions and in the presence of the target neurotoxin. These protocols allowed the evaluation of the peptide's effects on the activation and inactivation kinetics of the Naᵥ channels, as well as its overall impact on sodium currents.The results showed that at a concentration of 200 nM, Tf3 exhibited no significant effects on Naᵥ1.2 and Naᵥ1.6. However, at the same concentration, it demonstrated modulation of activation and total current parameters in the Naᵥ1.7 isoform. This work provides new insights into Tf3's specificity and may contribute to uncovering its mechanism of action, paving the way for the development of sodium channel modulators with potential applications in neurological disorder treatments and analgesic development.