Elsevier

Toxicon

Volume 119, 1 September 2016, Pages 253-265
Toxicon

Review
Potassium channel blockers from the venom of the Brazilian scorpion Tityus serrulatus (Lutz and Mello, 1922)

https://doi.org/10.1016/j.toxicon.2016.06.016Get rights and content

Highlights

  • The venom from the Brazilian scorpion Tityus serrulatus contains small peptidic toxins able to block various K+ channels.

  • Toxins from the external side structurally obstruct the K+ channel’s conducting pore.

  • The structures and mechanisms of action of the toxin-blockers so far identified in the Tityus serrulatus venom are analyzed.

  • Recent proteomic and transcriptomic data are correlated with previous biochemical results and discussed.

Abstract

Potassium (K+) channels are trans-membrane proteins, which play a key role in cellular excitability and signal transduction pathways. Scorpion toxins blocking the ion-conducting pore from the external side have been invaluable probes to elucidate the structural, functional, and physio-pathological characteristics of these ion channels. This review will focus on the interaction between K+ channels and their peptide blockers isolated from the venom of the scorpion Tityus serrulatus, which is considered as the most dangerous scorpion in Brazil, in particular in Minas-Gerais State, where many casualties are described each year. The primary mechanisms of action of these K+ blockers will be discussed in correlation with their structure, very often non-canonical compared to those of other well known K+ channels blockers purified from other scorpion venoms. Also, special attention will be brought to the most recent data obtained by proteomic and transcriptomic analyses on Tityus serrulatus venoms and venom glands.

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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      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).

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