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.

For decades, the study of venomous animals has focused on the isolation and biochemical characterization of specific venom components that have medical or biotechnological importance. Indeed, scorpions have been extensively studied under this optics, which has led to the identification of hundreds of different transcripts encoding toxic peptides. However, scorpions are interesting organisms not only because of their toxin diversity but also because they represent the most ancient terrestrial animals that fossil records have identified. About 2,000 species have been described around the world, which also implies that scorpions are extremely well-adapted arthropods that have managed to survive in different environmental conditions. Even though the divergence timing of scorpions places them as interesting model organisms for evolutionary inferences, little is known about the genomic organization, speciation events, and population dynamics of these arthropods. Different “omic” approaches have become a very powerful strategy for understanding the complexity of venomous animals. Transcriptomics, in particular, has been widely used to explore the transcriptional diversity of venom glands of several scorpion species. Recently, high-throughput sequencing platforms have substantially improved our capacity to describe biological features of scorpions but, most importantly, have outlined new directions toward a more complete understanding of the evolution of these arthropods. In this chapter, those transcriptomic strategies followed in the last two decades that went from cDNA cloning to next-generation sequencing methods will be described. Some biological and evolutionary questions about scorpion speciation and venom diversification will also be addressed. Finally, an attempt to raise some future directions in the field will be made.

Hundreds of toxins, particularly from scorpions of lesser medical significance, remain unknown, especially those from species endemic to specific ecosystems, such as Tityus fasciolatus. Their discovery could contribute to the development of new drugs for channelopathies and other diseases. Tf5 is a new peptide that has been identified from the venom of Tityus fasciolatus, a scorpion species endemic to the Brazilian Cerrado ecosystem. A full-length cDNA sequence of the Tf5 gene was obtained through a previously constructed transcriptomic library, where an ORF (Open Reading Frame) sequence with a length of 180 was found, including the 37 aa mature KTx domain, which has six Cys residues. Tf5 was purified from the crude venom, resulting in a peptide with a molecular mass of 3983.95 Da. Its K⁺ channel blocker activity was evaluated on Kv1.1, Kv1.2, Kv1.3, and Kv1.4 subtypes. Of these Kv channels, the peptide demonstrated an ability to block Kv1.2 and Kv1.3 with an IC₅₀ of 15.53 nM and 116.41 nM, respectively. Additionally, Tf5 shares a high degree of sequence identity with toxins from the α-KTx4 subfamily, which led to it being classified as α-KTx4.9. This is the first Kv channel blocker described from the T. fasciolatus scorpion.