ReviewPotassium channel blockers from the venom of the Brazilian scorpion Tityus serrulatus (Lutz and Mello, 1922)
Section snippets
The Tityus serrulatus venom and its toxins
Scorpions belong to an ancient and ecologically successful group of animals being exemplified in the fossil record to the Silurian era (430 million years ago) and currently comprising around 2000 known species (Lourenço, 2015a).
Their venoms are very complex mixtures of peptides, among other compounds, which display different kinds of biological activity. These venoms have been studied in the light of their pharmacological targets and their constituents are mainly able to bind specifically to
K+ channels targeted by Tityus serrulatus toxins
The very first scorpion toxin shown to block voltage-dependent K+ currents in the squid giant axon was Noxiustoxin (NTX), a 39 amino acid peptide purified from the venom of the “New-World” Mexican scorpion Centruroides noxius (Carbone et al., 1982). Currently, the literature has described more than one hundred twenty K+ channels blockers, isolated from scorpion venoms and classified into around 22 families (Cologna et al., 2011).
These scorpion toxins [KTxs, according to(Tytgat et al., 1999)]
Use of proteomic to study the Tityus serrulatus toxins
Mass spectrometry was used for the first time to analyse a whole scorpion venom content, in order to highlight its molecular composition and to facilitate the search for novel pharmacologically active compounds (Pimenta et al., 2001). The Tityus serrulatus venom was used for this leading characterization. A total of 380 different compounds were found in the two toxic fractions investigated.
Two fractions, previously separated by gel filtration according to their molecular size, were studied
Conclusion
In this review were highlighted the most recent knowledge on K+ channels blockers described in the Tityus serrulatus venom, which is responsible for many accidents of medical relevance in Brazil. Beside the historical side of their first identification and nomenclature, the last chemical and pharmacological characterizations of these compounds were discussed, combined with the advent of different sophisticated techniques, as mass spectrometry. Some questions could be rise. As an example: is the
Ethical statement
This article does not include any studies using human subjects. Authors declare that the described work has not been published previously. All authors approve this manuscript.
Conflict of interest
All authors declare that they have no conflict of interest.
Acknowledgments
We would like to thank CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) from Brazil for supporting a binational project (Brazil-France 407332/2013-8) in toxins.
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Unraveling and profiling Tityus bahiensis venom: Biochemical analyses of the major toxins
2023, Journal of ProteomicsHeterologous expression of Ts8, a neurotoxin from Tityus serrulatus venom, evidences its antifungal activity
2022, ToxiconCitation Excerpt :We believe that rTs8-FragII, when produced by P. pastoris, is readily cleaved to minimize its toxicity to P. pastoris cells, which would explain why the smaller fragment, rTs8-FragI (major product of proteolytic activity in amount) had no activity in this assay. The native toxin Ts8-propeptide is Ts8 with eight more amino acids in the N-terminal site (Martin-Eauclaire et al., 2016), which can explain the higher antimicrobial activity when compared to Ts8 alone (Fig. 5). An extended N-terminal can affect TsTXKβ and rMeuTXKβ1 activity in K+ channel, however, it is related to cytolytic and antimicrobial toxin activity (Almeida et al., 2013; Zhu et al., 2010).
The effects of Tityus bahiensis scorpion venom on the contractility of jejunum, vas deferens, and the aorta is differentially affected by tetrodotoxin
2021, ToxiconCitation Excerpt :Only in the aorta, the relaxation was resistant to tetrodotoxin. Venoms of scorpions of the Tityus genus are a mix of several neurotoxins that act on voltage-gated sodium and potassium channels (Cologna et al., 2009; Jiménez-Vargas et al., 2017; Martin-Eauclaire et al., 2016). The final effect of these toxins is the release of neurotransmitters, mainly a massive release of mediators from the autonomic nervous system (Cologna et al., 2009; Cupo, 2015; Isbister and Bawaskar, 2014; Massensini et al., 2003; Pucca et al., 2015).
Immunomodulatory and protective effects of interleukin-4 on the neuropathological alterations induced by a potassium channel blocker
2021, Journal of NeuroimmunologyCitation Excerpt :These channels play a major role in neuronal excitability; it contributes to membrane repolarization, thus limiting the neuronal excitability. Based on this function, several biomolecules as K+ channel blockers are used in experimental models to induce seizures (Martin-Eauclaire et al., 2016; Mourre et al., 1997; Pena and Tapia, 2000). Our previous studies showed that the use of Kaliotoxin (KTx) a specific Kv1.1 and Kv1.3 voltage potassium blocker neurotoxin isolated from Androctonus australis hector (Aah) scorpion venom, can induce seizures and neuroinflammatory response (Ladjel-Mendil et al., 2013; Laraba-Djebari et al., 1994; Meki et al., 2000; Sifi et al., 2016; Taibi-Djennah et al., 2015).
Effect of Tityus serrulatus scorpion venom on isolated jejunum: A very useful tool to study the interaction between neurons in the enteric nervous system
2020, Autonomic Neuroscience: Basic and ClinicalCitation Excerpt :Voltage-gated Na+ (Cestèle and Catterall, 2000) and K+ (Garcia et al., 1999; Possani et al., 1999; Zhu et al., 2004) channels are the more frequent targets of scorpion toxins, but different types of Ca++ (Housley et al., 2017) and Cl− (Ojeda et al., 2016; Thompson et al., 2009) channels are also modulated by some scorpion toxins. Tityus serrulatus belonging to the Buthidae family and its venom contains Na+- and K+-channel toxins (Cologna et al., 2009; Jiménez-Vargas et al., 2017; Martin-Eauclaire et al., 2016). Virtually all symptoms of envenomation by this scorpion are attributed to the presence of these toxins that drive the autonomic nervous system to a massive release of neurotransmitters (Cologna et al., 2009; Cupo, 2015; Isbister and Bawaskar, 2014; Massensini et al., 2003; Pucca et al., 2015).