Skip to main content
SpringerLink
Log in

Potassium Channel-Blocking Peptide Toxins from Scorpion Venom

  • Living reference work entry
  • First Online:
Scorpion Venoms

  • 388 Accesses

Abstract

In the last three decades, numerous peptides isolated from scorpion venom have been identified as members of the KTx, or potassium channel-blocking group of toxins. This chapter provides an overview of the four families of KTx, named α, β, γ, and κ, discussing characteristic structural features and K+ channel selectivity of these peptides. Methods of KTx peptide identification and isolation, as well as techniques for the assessment of the efficacy of potassium channel blockade, are described. With the advancement of molecular biology, molecular dynamics simulations, and nuclear magnetic resonance (NMR) techniques, many details of the toxin-channel interaction have been clarified and models of different modes of toxin binding have emerged. A table summarizing all currently known 133 members of the KTx group of peptides is presented, including their systematic and common names, along with their affinities for the major target K+ channels, which may be in the low picomolar range. These peptides have provided vital information about the topology of the external pore region of K+ channels highlighting similarities and even minute differences. In addition to being valuable exploratory molecular tools, peptide blockers of K+ channels with high affinity and selectivity offer great potential for therapeutic use in a wide variety of diseases as was illustrated by several successful trials in animal models.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Abbas N, Belghazi M, Abdel-Mottaleb Y, Tytgat J, Bougis PE, Martin-Eauclaire MF. A new Kaliotoxin selective towards Kv1.3 and Kv1.2 but not Kv1.1 channels expressed in oocytes. Biochem Biophys Res Commun. 2008;376(3):525–30.

    CAS  PubMed  Google Scholar 

  • Abdel-Mottaleb Y, Clynen E, Jalali A, Bosmans F, Vatanpour H, Schoofs L, et al. The first potassium channel toxin from the venom of the Iranian scorpion Odonthobuthus doriae. FEBS Lett. 2006;580(26):6254–8.

    CAS  PubMed  Google Scholar 

  • Abdel-Mottaleb Y, Vandendriessche T, Clynen E, Landuyt B, Jalali A, Vatanpour H, et al. OdK2, a Kv1.3 channel-selective toxin from the venom of the Iranian scorpion Odonthobuthus doriae. Toxicon. 2008;51(8):1424–30.

    CAS  PubMed  Google Scholar 

  • Aiyar J, Withka JM, Rizzi JP, Singleton DH, Andrews GC, Lin W, et al. Topology of the pore-region of a K+ channel revealed by the NMR-derived structures of scorpion toxins. Neuron. 1995;15(5):1169–81.

    CAS  PubMed  Google Scholar 

  • Auguste P, Hugues M, Grave B, Gesquiere JC, Maes P, Tartar A, et al. Leiurotoxin I (scyllatoxin), a peptide ligand for Ca2(+)-activated K+ channels. Chemical synthesis, radiolabeling, and receptor characterization. J Biol Chem. 1990;265(8):4753–9.

    CAS  PubMed  Google Scholar 

  • Bagdany M, Batista CV, Valdez-Cruz NA, Somodi S, Rodriguez de la Vega RC, Licea AF, et al. Anuroctoxin, a new scorpion toxin of the alpha-KTx 6 subfamily, is highly selective for Kv1.3 over IKCa1 ion channels of human T lymphocytes. Mol Pharmacol. 2005;67(4):1034–44.

    CAS  PubMed  Google Scholar 

  • Barona J, Batista CV, Zamudio FZ, Gomez-Lagunas F, Wanke E, Otero R, et al. Proteomic analysis of the venom and characterization of toxins specific for Na+ - and K+ -channels from the Colombian scorpion Tityus pachyurus. Biochim Biophys Acta. 2006;1764(1):76–84.

    CAS  PubMed  Google Scholar 

  • Bartok A, Panyi G, Domingos Possani L, Varga Z. Molecular determinants of selectivity for Kv1.3 K+ channels. Biophys J. 2013;104(2):465a.

    Google Scholar 

  • Bartok A, Toth A, Hajdu P, Varga Z, Panyi G. Margatoxin is a nonselective inhibitor of Kv1.3 channels – a comprehensive study. Biophys J. 2014;106(2):551a–2.

    Google Scholar 

  • Bartschat DK, Blaustein MP. Potassium channels in isolated presynaptic nerve terminals from rat brain. J Physiol. 1985;361:419–40.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Batista CV, Gomez-Lagunas F, Lucas S, Possani LD. Tc1, from Tityus cambridgei, is the first member of a new subfamily of scorpion toxin that blocks K(+)-channels. FEBS Lett. 2000;486(2):117–20.

    CAS  PubMed  Google Scholar 

  • Batista CV, Gomez-Lagunas F, Rodriguez de la Vega RC, Hajdu P, Panyi G, Gaspar R, et al. Two novel toxins from the Amazonian scorpion Tityus cambridgei that block Kv1.3 and Shaker B K(+)-channels with distinctly different affinities. Biochim Biophys Acta. 2002;1601(2):123–31.

    CAS  PubMed  Google Scholar 

  • Batista CV, Roman-Gonzalez SA, Salas-Castillo SP, Zamudio FZ, Gomez-Lagunas F, Possani LD. Proteomic analysis of the venom from the scorpion Tityus stigmurus: biochemical and physiological comparison with other Tityus species. Comp Biochem Physiol C Toxicol Pharmacol. 2007;146(1–2):147–57.

    CAS  PubMed  Google Scholar 

  • Beeton C, Wulff H, Barbaria J, Clot-Faybesse O, Pennington M, Bernard D, et al. Selective blockade of T lymphocyte K(+) channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Proc Natl Acad Sci U S A. 2001;98(24):13942–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Beeton C, Wulff H, Standifer NE, Azam P, Mullen KM, Pennington MW, et al. Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc Natl Acad Sci U S A. 2006;103(46):17414–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bontems F, Roumestand C, Boyot P, Gilquin B, Doljansky Y, Menez A, et al. Three-dimensional structure of natural charybdotoxin in aqueous solution by 1H-NMR. Charybdotoxin possesses a structural motif found in other scorpion toxins. Eur J Biochem. 1991;196(1):19–28.

    CAS  PubMed  Google Scholar 

  • Bontems F, Gilquin B, Roumestand C, Menez A, Toma F. Analysis of side-chain organization on a refined model of charybdotoxin: structural and functional implications. Biochemistry. 1992;31(34):7756–64.

    CAS  PubMed  Google Scholar 

  • Caldwell JE, Abildgaard F, Dzakula Z, Ming D, Hellekant G, Markley JL. Solution structure of the thermostable sweet-tasting protein brazzein. Nat Struct Biol. 1998;5(6):427–31.

    CAS  PubMed  Google Scholar 

  • Camargos TS, Restano-Cassulini R, Possani LD, Peigneur S, Tytgat J, Schwartz CA, et al. The new kappa-KTx 2.5 from the scorpion Opisthacanthus cayaporum. Peptides. 2011;32(7):1509–17.

    CAS  PubMed  Google Scholar 

  • Cao Z, Xiao F, Peng F, Jiang D, Mao X, Liu H, et al. Expression, purification and functional characterization of a recombinant scorpion venom peptide BmTXKbeta. Peptides. 2003;24(2):187–92.

    CAS  PubMed  Google Scholar 

  • Carbone E, Wanke E, Prestipino G, Possani LD, Maelicke A. Selective blockage of voltage-dependent K+ channels by a novel scorpion toxin. Nature. 1982;296(5852):90–1.

    CAS  PubMed  Google Scholar 

  • Castle NA, London DO, Creech C, Fajloun Z, Stocker JW, Sabatier JM. Maurotoxin: a potent inhibitor of intermediate conductance Ca2+ -activated potassium channels. Mol Pharmacol. 2003;63(2):409–18.

    CAS  PubMed  Google Scholar 

  • Chen ZY, Zeng DY, Hu YT, He YW, Pan N, Ding JP, et al. Structural and functional diversity of acidic scorpion potassium channel toxins. PLoS One. 2012;7(4):e35154.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cologna CT, Peigneur S, Rosa JC, Selistre-de-Araujo HS, Varanda WA, Tytgat J, et al. Purification and characterization of Ts15, the first member of a new alpha-KTX subfamily from the venom of the Brazilian scorpion Tityus serrulatus. Toxicon. 2011;58(1):54–61.

    CAS  PubMed  Google Scholar 

  • Conde R, Zamudio FZ, Rodriguez MH, Possani LD. Scorpine, an anti-malaria and anti-bacterial agent purified from scorpion venom. FEBS Lett. 2000;471(2–3):165–8.

    CAS  PubMed  Google Scholar 

  • Coronas FV, de Roodt AR, Portugal TO, Zamudio FZ, Batista CV, Gomez-Lagunas F, et al. Disulfide bridges and blockage of Shaker B K(+)-channels by another butantoxin peptide purified from the Argentinean scorpion Tityus trivittatus. Toxicon. 2003;41(2):173–9.

    CAS  PubMed  Google Scholar 

  • Corzo G, Papp F, Varga Z, Barraza O, Espino-Solis PG, Rodriguez de la Vega RC, et al. A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus. Biochem Pharmacol. 2008;76(9):1142–54.

    CAS  PubMed  Google Scholar 

  • Crest M, Jacquet G, Gola M, Zerrouk H, Benslimane A, Rochat H, et al. Kaliotoxin, a novel peptidyl inhibitor of neuronal BK-type Ca(2+)-activated K+ channels characterized from Androctonus mauretanicus mauretanicus venom. J Biol Chem. 1992;267(3):1640–7.

    CAS  PubMed  Google Scholar 

  • Dauplais M, Lecoq A, Song J, Cotton J, Jamin N, Gilquin B, et al. On the convergent evolution of animal toxins. Conservation of a diad of functional residues in potassium channel-blocking toxins with unrelated structures. J Biol Chem. 1997;272(7):4302–9.

    CAS  PubMed  Google Scholar 

  • Dhawan R, Varshney A, Mathew MK, Lala AK. BTK-2, a new inhibitor of the Kv1.1 potassium channel purified from Indian scorpion Buthus tamulus. FEBS Lett. 2003;539(1–3):7–13.

    CAS  PubMed  Google Scholar 

  • Diego-Garcia E, Abdel-Mottaleb Y, Schwartz EF, de la Vega RC, Tytgat J, Possani LD. Cytolytic and K+ channel blocking activities of beta-KTx and scorpine-like peptides purified from scorpion venoms. Cell Mol Life Sci. 2008;65(1):187–200.

    CAS  PubMed  Google Scholar 

  • Dimarcq JL, Bulet P, Hetru C, Hoffmann J. Cysteine-rich antimicrobial peptides in invertebrates. Biopolymers. 1998;47(6):465–77.

    CAS  PubMed  Google Scholar 

  • D’Suze G, Zamudio F, Gomez-Lagunas F, Possani LD. A novel K+ channel blocking toxin from Tityus discrepans scorpion venom. FEBS Lett. 1999;456(1):146–8.

    PubMed  Google Scholar 

  • D’Suze G, Batista CV, Frau A, Murgia AR, Zamudio FZ, Sevcik C, et al. Discrepin, a new peptide of the sub-family alpha-ktx15, isolated from the scorpion Tityus discrepans irreversibly blocks K+ -channels (IA currents) of cerebellum granular cells. Arch Biochem Biophys. 2004;430(2):256–63.

    PubMed  Google Scholar 

  • Dudina EE, Korolkova YV, Bocharova NE, Koshelev SG, Egorov TA, Huys I, et al. OsK2, a new selective inhibitor of Kv1.2 potassium channels purified from the venom of the scorpion Orthochirus scrobiculosus. Biochem Biophys Res Commun. 2001;286(5):841–7.

    CAS  PubMed  Google Scholar 

  • Gao B, Peigneur S, Tytgat J, Zhu S. A potent potassium channel blocker from Mesobuthus eupeus scorpion venom. Biochimie. 2010;92(12):1847–53.

    CAS  PubMed  Google Scholar 

  • Garcia ML, Garcia-Calvo M, Hidalgo P, Lee A, MacKinnon R. Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom. Biochemistry. 1994;33(22):6834–9.

    CAS  PubMed  Google Scholar 

  • Garcia-Valdes J, Zamudio FZ, Toro L, Possani LD. Slotoxin, alphaKTx1.11, a new scorpion peptide blocker of MaxiK channels that differentiates between alpha and alpha+beta (beta1 or beta4) complexes. FEBS Lett. 2001;505(3):369–73.

    CAS  PubMed  Google Scholar 

  • Goldstein SA, Pheasant DJ, Miller C. The charybdotoxin receptor of a Shaker K+ channel: peptide and channel residues mediating molecular recognition. Neuron. 1994;12(6):1377–88.

    CAS  PubMed  Google Scholar 

  • Gomez-Lagunas F, Olamendi-Portugal T, Zamudio FZ, Possani LD. Two novel toxins from the venom of the scorpion Pandinus imperator show that the N-terminal amino acid sequence is important for their affinities towards Shaker B K+ channels. J Membr Biol. 1996;152(1):49–56.

    CAS  PubMed  Google Scholar 

  • Gomez-Lagunas F, Olamendi-Portugal T, Possani LD. Block of ShakerB K+ channels by Pi1, a novel class of scorpion toxin. FEBS Lett. 1997;400(2):197–200.

    CAS  PubMed  Google Scholar 

  • Grissmer S, Nguyen AN, Aiyar J, Hanson DC, Mather RJ, Gutman GA, et al. Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol. 1994;45(6):1227–34.

    CAS  PubMed  Google Scholar 

  • Huys I, Dyason K, Waelkens E, Verdonck F, van Zyl J, du Plessis J, et al. Purification, characterization and biosynthesis of parabutoxin 3, a component of Parabuthus transvaalicus venom. Eur J Biochem. 2002;269(7):1854–65.

    CAS  PubMed  Google Scholar 

  • Huys I, Xu CQ, Wang CZ, Vacher H, Martin-Eauclaire MF, Chi CW, et al. BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents. Biochem J. 2004a;378(Pt 3):745–52.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huys I, Olamendi-Portugal T, Garcia-Gomez BI, Vandenberghe I, Van Beeumen J, Dyason K, et al. A subfamily of acidic alpha-K(+) toxins. J Biol Chem. 2004b;279(4):2781–9.

    CAS  PubMed  Google Scholar 

  • Jouirou B, Mosbah A, Visan V, Grissmer S, M’Barek S, Fajloun Z, et al. Cobatoxin 1 from Centruroides noxius scorpion venom: chemical synthesis, three-dimensional structure in solution, pharmacology and docking on K+ channels. Biochem J. 2004;377(Pt 1):37–49.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kharrat R, Mansuelle P, Sampieri F, Crest M, Oughideni R, Van Rietschoten J, et al. Maurotoxin, a four disulfide bridge toxin from Scorpio maurus venom: purification, structure and action on potassium channels. FEBS Lett. 1997;406(3):284–90.

    CAS  PubMed  Google Scholar 

  • Koch RO, Wanner SG, Koschak A, Hanner M, Schwarzer C, Kaczorowski GJ, et al. Complex subunit assembly of neuronal voltage-gated K+ channels. Basis for high-affinity toxin interactions and pharmacology. J Biol Chem. 1997;272(44):27577–81.

    CAS  PubMed  Google Scholar 

  • Korolkova YV, Kozlov SA, Lipkin AV, Pluzhnikov KA, Hadley JK, Filippov AK, et al. An ERG channel inhibitor from the scorpion Buthus eupeus. J Biol Chem. 2001;276(13):9868–76.

    CAS  PubMed  Google Scholar 

  • Koschak A, Bugianesi RM, Mitterdorfer J, Kaczorowski GJ, Garcia ML, Knaus HG. Subunit composition of brain voltage-gated potassium channels determined by hongotoxin-1, a novel peptide derived from Centruroides limbatus venom. J Biol Chem. 1998;273(5):2639–44.

    CAS  PubMed  Google Scholar 

  • Koshy S, Wu D, Hu X, Tajhya RB, Huq R, Khan FS, et al. Blocking KCa3.1 channels increases tumor cell killing by a subpopulation of human natural killer lymphocytes. PLoS One. 2013;8(10):e76740.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Koshy S, Huq R, Tanner MR, Atik MA, Porter PC, Khan FS, et al. Blocking Kv1.3 channels inhibits Th2 lymphocyte function and treats a rat model of asthma. J Biol Chem. 2014;289(18):12623.

    CAS  PubMed  Google Scholar 

  • Kozminsky-Atias A, Somech E, Zilberberg N. Isolation of the first toxin from the scorpion Buthus occitanus israelis showing preference for Shaker potassium channels. FEBS Lett. 2007;581(13):2478–84.

    CAS  PubMed  Google Scholar 

  • Landoulsi Z, Miceli F, Palmese A, Amoresano A, Marino G, El Ayeb M, et al. Subtype-selective activation of K(v)7 channels by AaTXKbeta(2)(-)(6)(4), a novel toxin variant from the Androctonus australis scorpion venom. Mol Pharmacol. 2013;84(5):763–73.

    CAS  PubMed  Google Scholar 

  • Lange A, Giller K, Hornig S, Martin-Eauclaire MF, Pongs O, Becker S, et al. Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR. Nature. 2006;440(7086):959–62.

    CAS  PubMed  Google Scholar 

  • Laraba-Djebari F, Legros C, Crest M, Ceard B, Romi R, Mansuelle P, et al. The kaliotoxin family enlarged. Purification, characterization, and precursor nucleotide sequence of KTX2 from Androctonus australis venom. J Biol Chem. 1994;269(52):32835–43.

    CAS  PubMed  Google Scholar 

  • Lebrun B, Romi-Lebrun R, Martin-Eauclaire MF, Yasuda A, Ishiguro M, Oyama Y, et al. A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrus spinnifer (Scorpionidae) venom. Biochem J. 1997;328(Pt 1):321–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Legros C, Oughuideni R, Darbon H, Rochat H, Bougis PE, Martin-Eauclaire MF. Characterization of a new peptide from Tityus serrulatus scorpion venom which is a ligand of the apamin-binding site. FEBS Lett. 1996;390(1):81–4.

    CAS  PubMed  Google Scholar 

  • Li MH, Zhang NX, Chen XQ, Wu G, Wu HM, Hu GY. BmKK4, a novel toxin from the venom of Asian scorpion Buthus martensii Karsch, inhibits potassium currents in rat hippocampal neurons in vitro. Toxicon. 2003;42(2):199–205.

    CAS  PubMed  Google Scholar 

  • Liu J, Ma Y, Yin S, Zhao R, Fan S, Hu Y, et al. Molecular cloning and functional identification of a new K(+) channel blocker, LmKTx10, from the scorpion Lychas mucronatus. Peptides. 2009;30(4):675–80.

    CAS  PubMed  Google Scholar 

  • Lucchesi K, Ravindran A, Young H, Moczydlowski E. Analysis of the blocking activity of charybdotoxin homologs and iodinated derivatives against Ca2+-activated K+ channels. J Membr Biol. 1989;109(3):269–81.

    CAS  PubMed  Google Scholar 

  • Luna-Ramirez K, Bartok A, Restano-Cassulini R, Quintero-Hernandez V, Coronas F, Christensen J, et al. Structure, molecular modeling and function of the first potassium channel blocker, urotoxin, isolated from the venom of the Australian scorpion Urodacus yaschenkoi. Mol Pharmacol. 2014;86:28.

    PubMed  Google Scholar 

  • MacKinnon R, Latorre R, Miller C. Role of surface electrostatics in the operation of a high-conductance Ca2+ -activated K+ channel. Biochemistry. 1989;28(20):8092–9.

    CAS  PubMed  Google Scholar 

  • Mahjoubi-Boubaker B, Crest M, Khalifa RB, El Ayeb M, Kharrat R. Kbot1, a three disulfide bridges toxin from Buthus occitanus tunetanus venom highly active on both SK and Kv channels. Peptides. 2004;25(4):637–45.

    CAS  PubMed  Google Scholar 

  • Mao X, Cao Z, Yin S, Ma Y, Wu Y, Li W. Cloning and characterization of BmK86, a novel K+ -channel blocker from scorpion venom. Biochem Biophys Res Commun. 2007;360(4):728–34.

    CAS  PubMed  Google Scholar 

  • Markovic-Plese S, Cortese I, Wandinger KP, McFarland HF, Martin R. CD4 + CD28- costimulation-independent T cells in multiple sclerosis. J Clin Invest. 2001;108(8):1185–94.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Martin BM, Ramirez AN, Gurrola GB, Nobile M, Prestipino G, Possani LD. Novel K(+)-channel-blocking toxins from the venom of the scorpion Centruroides limpidus limpidus Karsch. Biochem J. 1994;304(Pt 1):51–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  • M’Barek S, Mosbah A, Sandoz G, Fajloun Z, Olamendi-Portugal T, Rochat H, et al. Synthesis and characterization of Pi4, a scorpion toxin from Pandinus imperator that acts on K+ channels. Eur J Biochem. 2003;270(17):3583–92.

    PubMed  Google Scholar 

  • Meera P, Wallner M, Toro L. A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+ -activated K+ channel resistant to charybdotoxin and iberiotoxin. Proc Natl Acad Sci U S A. 2000;97(10):5562–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Meki A, Mansuelle P, Laraba-Djebari F, Oughideni R, Rochat H, Martin-Eauclaire MF. KTX3, the kaliotoxin from Buthus occitanus tunetanus scorpion venom: one of an extensive family of peptidyl ligands of potassium channels. Toxicon. 2000;38(1):105–11.

    CAS  PubMed  Google Scholar 

  • Menez A. Functional architectures of animal toxins: a clue to drug design? Toxicon. 1998;36(11):1557–72.

    CAS  PubMed  Google Scholar 

  • Miller C. Competition for block of a Ca2(+)-activated K+ channel by charybdotoxin and tetraethylammonium. Neuron. 1988;1(10):1003–6.

    CAS  PubMed  Google Scholar 

  • Mouhat S, Mosbah A, Visan V, Wulff H, Delepierre M, Darbon H, et al. The ‘functional’ dyad of scorpion toxin Pi1 is not itself a prerequisite for toxin binding to the voltage-gated Kv1.2 potassium channels. Biochem J. 2004;377(Pt 1):25–36.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mouhat S, Visan V, Ananthakrishnan S, Wulff H, Andreotti N, Grissmer S, et al. K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpion venom. Biochem J. 2005;385(Pt 1):95–104.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mourre C, Chernova MN, Martin-Eauclaire MF, Bessone R, Jacquet G, Gola M, et al. Distribution in rat brain of binding sites of kaliotoxin, a blocker of Kv1.1 and Kv1.3 alpha-subunits. J Pharmacol Exp Ther. 1999;291(3):943–52.

    CAS  PubMed  Google Scholar 

  • Nastainczyk W, Meves H, Watt DD. A short-chain peptide toxin isolated from Centruroides sculpturatus scorpion venom inhibits ether-a-go-go-related gene K(+) channels. Toxicon. 2002;40(7):1053–8.

    CAS  PubMed  Google Scholar 

  • Nieto AR, Gurrola GB, Vaca L, Possani LD. Noxiustoxin 2, a novel K+ channel blocking peptide from the venom of the scorpion Centruroides noxius Hoffmann. Toxicon. 1996;34(8):913–22.

    CAS  PubMed  Google Scholar 

  • Noda M, Takahashi H, Tanabe T, Toyosato M, Furutani Y, Hirose T, et al. Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence. Nature. 1982;299(5886):793–7.

    CAS  PubMed  Google Scholar 

  • Noda M, Shimizu S, Tanabe T, Takai T, Kayano T, Ikeda T, et al. Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence. Nature. 1984;312(5990):121–7.

    CAS  PubMed  Google Scholar 

  • Novello JC, Arantes EC, Varanda WA, Oliveira B, Giglio JR, Marangoni S. TsTX-IV, a short chain four-disulfide-bridged neurotoxin from Tityus serrulatus venom which acts on Ca2+ -activated K+ channels. Toxicon. 1999;37(4):651–60.

    CAS  PubMed  Google Scholar 

  • Olamendi-Portugal T, Gomez-Lagunas F, Gurrola GB, Possani LD. Two similar peptides from the venom of the scorpion Pandinus imperator, one highly effective blocker and the other inactive on K+ channels. Toxicon. 1998;36(5):759–70.

    CAS  PubMed  Google Scholar 

  • Olamendi-Portugal T, Somodi S, Fernandez JA, Zamudio FZ, Becerril B, Varga Z, et al. Novel alpha-KTx peptides from the venom of the scorpion Centruroides elegans selectively blockade Kv1.3 over IKCa1 K+ channels of T cells. Toxicon. 2005;46(4):418–29.

    CAS  PubMed  Google Scholar 

  • Papp F, Batista CV, Varga Z, Herceg M, Roman-Gonzalez SA, Gaspar R, et al. Tst26, a novel peptide blocker of Kv1.2 and Kv1.3 channels from the venom of Tityus stigmurus. Toxicon. 2009;54(4):379–89.

    CAS  PubMed  Google Scholar 

  • Pardo-Lopez L, Zhang M, Liu J, Jiang M, Possani LD, Tseng GN. Mapping the binding site of a human ether-a-go-go-related gene-specific peptide toxin (ErgTx) to the channel’s outer vestibule. J Biol Chem. 2002;277(19):16403–11.

    CAS  PubMed  Google Scholar 

  • Pedarzani P, D’Hoedt D, Doorty KB, Wadsworth JD, Joseph JS, Jeyaseelan K, et al. Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+-activated K+ channels and afterhyperpolarization currents in central neurons. J Biol Chem. 2002;277(48):46101–9.

    CAS  PubMed  Google Scholar 

  • Peter Jr M, Hajdu P, Varga Z, Damjanovich S, Possani LD, Panyi G, et al. Blockage of human T lymphocyte Kv1.3 channels by Pi1, a novel class of scorpion toxin. Biochem Biophys Res Commun. 2000;278(1):34–7.

    CAS  PubMed  Google Scholar 

  • Peter Jr M, Varga Z, Hajdu P, Gaspar Jr R, Damjanovich S, Horjales E, et al. Effects of toxins Pi2 and Pi3 on human T lymphocyte Kv1.3 channels: the role of Glu7 and Lys24. J Membr Biol. 2001;179(1):13–25.

    CAS  PubMed  Google Scholar 

  • Pisciotta M, Coronas FI, Bloch C, Prestipino G, Possani LD. Fast K(+) currents from cerebellum granular cells are completely blocked by a peptide purified from Androctonus australis Garzoni scorpion venom. Biochim Biophys Acta. 2000;1468(1–2):203–12.

    CAS  PubMed  Google Scholar 

  • Ranganathan R, Lewis JH, MacKinnon R. Spatial localization of the K+ channel selectivity filter by mutant cycle-based structure analysis. Neuron. 1996;16(1):131–9.

    CAS  PubMed  Google Scholar 

  • Rauer H, Lanigan MD, Pennington MW, Aiyar J, Ghanshani S, Cahalan MD, et al. Structure-guided transformation of charybdotoxin yields an analog that selectively targets Ca(2+)-activated over voltage-gated K(+) channels. J Biol Chem. 2000;275(2):1201–8.

    CAS  PubMed  Google Scholar 

  • Regaya I, Beeton C, Ferrat G, Andreotti N, Darbon H, De Waard M, et al. Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins. J Biol Chem. 2004;279(53):55690–6.

    CAS  PubMed  Google Scholar 

  • Restano-Cassulini R, Korolkova YV, Diochot S, Gurrola G, Guasti L, Possani LD, et al. Species diversity and peptide toxins blocking selectivity of ether-a-go-go-related gene subfamily K+ channels in the central nervous system. Mol Pharmacol. 2006;69(5):1673–83.

    CAS  PubMed  Google Scholar 

  • Restano-Cassulini R, Olamendi-Portugal T, Zamudio F, Becerril B, Possani LD. Two novel ergtoxins, blockers of K+-channels, purified from the Mexican scorpion Centruroides elegans elegans. Neurochem Res. 2008;33(8):1525–33.

    CAS  PubMed  Google Scholar 

  • Rodriguez de la Vega RC, Merino E, Becerril B, Possani LD. Novel interactions between K+ channels and scorpion toxins. Trends Pharmacol Sci. 2003;24(5):222–7.

    CAS  PubMed  Google Scholar 

  • Rogowski RS, Krueger BK, Collins JH, Blaustein MP. Tityustoxin K alpha blocks voltage-gated noninactivating K+ channels and unblocks inactivating K+ channels blocked by alpha-dendrotoxin in synaptosomes. Proc Natl Acad Sci U S A. 1994;91(4):1475–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rogowski RS, Collins JH, O’Neill TJ, Gustafson TA, Werkman TR, Rogawski MA, et al. Three new toxins from the scorpion Pandinus imperator selectively block certain voltage-gated K+ channels. Mol Pharmacol. 1996;50(5):1167–77.

    CAS  PubMed  Google Scholar 

  • Romi R, Crest M, Gola M, Sampieri F, Jacquet G, Zerrouk H, et al. Synthesis and characterization of kaliotoxin. Is the 26-32 sequence essential for potassium channel recognition? J Biol Chem. 1993;268(35):26302–9.

    CAS  PubMed  Google Scholar 

  • Romi-Lebrun R, Lebrun B, Martin-Eauclaire MF, Ishiguro M, Escoubas P, Wu FQ, et al. Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels. Biochemistry. 1997a;36(44):13473–82.

    CAS  PubMed  Google Scholar 

  • Romi-Lebrun R, Martin-Eauclaire MF, Escoubas P, Wu FQ, Lebrun B, Hisada M, et al. Characterization of four toxins from Buthus martensi scorpion venom, which act on apamin-sensitive Ca2+-activated K+ channels. Eur J Biochem. 1997b;245(2):457–64.

    CAS  PubMed  Google Scholar 

  • Sabatier JM, Zerrouk H, Darbon H, Mabrouk K, Benslimane A, Rochat H, et al. P05, a new leiurotoxin I-like scorpion toxin: synthesis and structure-activity relationships of the alpha-amidated analog, a ligand of Ca(2+)-activated K+ channels with increased affinity. Biochemistry. 1993;32(11):2763–70.

    CAS  PubMed  Google Scholar 

  • Schwartz EF, Schwartz CA, Gomez-Lagunas F, Zamudio FZ, Possani LD. HgeTx1, the first K+ -channel specific toxin characterized from the venom of the scorpion Hadrurus gertschi Soleglad. Toxicon. 2006;48(8):1046–53.

    CAS  PubMed  Google Scholar 

  • Schwartz EF, Bartok A, Schwartz CA, Papp F, Gomez-Lagunas F, Panyi G, et al. OcyKTx2, a new K(+)-channel toxin characterized from the venom of the scorpion Opisthacanthus cayaporum. Peptides. 2013;46:40–6.

    CAS  PubMed  Google Scholar 

  • Selisko B, Garcia C, Becerril B, Gomez-Lagunas F, Garay C, Possani LD. Cobatoxins 1 and 2 from Centruroides noxius Hoffmann constitute a subfamily of potassium-channel-blocking scorpion toxins. Eur J Biochem. 1998;254(3):468–79.

    CAS  PubMed  Google Scholar 

  • Shi J, He HQ, Zhao R, Duan YH, Chen J, Chen Y, et al. Inhibition of martentoxin on neuronal BK channel subtype (alpha+beta4): implications for a novel interaction model. Biophys J. 2008;94(9):3706–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shieh CC, Coghlan M, Sullivan JP, Gopalakrishnan M. Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacol Rev. 2000;52(4):557–94.

    CAS  PubMed  Google Scholar 

  • Song WJ. Genes responsible for native depolarization-activated K+ currents in neurons. Neurosci Res. 2002;42(1):7–14.

    CAS  PubMed  Google Scholar 

  • Song WJ, Tkatch T, Baranauskas G, Ichinohe N, Kitai ST, Surmeier DJ. Somatodendritic depolarization-activated potassium currents in rat neostriatal cholinergic interneurons are predominantly of the A type and attributable to coexpression of Kv4.2 and Kv4.1 subunits. J Neurosci. 1998;18(9):3124–37.

    CAS  PubMed  Google Scholar 

  • Srairi-Abid N, Shahbazzadeh D, Chatti I, Mlayah-Bellalouna S, Mejdoub H, Borchani L, et al. Hemitoxin, the first potassium channel toxin from the venom of the Iranian scorpion Hemiscorpius lepturus. FEBS J. 2008;275(18):4641–50.

    CAS  PubMed  Google Scholar 

  • Srinivasan KN, Sivaraja V, Huys I, Sasaki T, Cheng B, Kumar TK, et al. kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity. J Biol Chem. 2002;277(33):30040–7.

    CAS  PubMed  Google Scholar 

  • Tajhya RB, Hu X, Tanner MR, Timchenko L, Beeton C. The functional switch in potassium channels in myotonic dystrophy type 1 impairs proliferation, migration and fusion during myogenesis. Biophys J. 2014;106(2):551a.

    Google Scholar 

  • Tanner MR, Hu X, Huq R, Laragione T, Tajhya RB, Horrigan FT, et al. Blocking KCa1.1 channels inhibits the pathogenic features of fibroblast-like synoviocytes and treats rat models of rheumatoid arthritis. Biophys J. 2014;106(2):550a–1.

    Google Scholar 

  • Thomma BP, Cammue BP, Thevissen K. Plant defensins. Planta. 2002;216(2):193–202.

    CAS  PubMed  Google Scholar 

  • Thompson CH, Olivetti PR, Fuller MD, Freeman CS, McMaster D, French RJ, et al. Isolation and characterization of a high affinity peptide inhibitor of ClC-2 chloride channels. J Biol Chem. 2009;284(38):26051–62.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Torres AM, Bansal P, Alewood PF, Bursill JA, Kuchel PW, Vandenberg JI. Solution structure of CnErg1 (Ergtoxin), a HERG specific scorpion toxin. FEBS Lett. 2003;539(1–3):138–42.

    CAS  PubMed  Google Scholar 

  • Uawonggul N, Thammasirirak S, Chaveerach A, Arkaravichien T, Bunyatratchata W, Ruangjirachuporn W, et al. Purification and characterization of Heteroscorpine-1 (HS-1) toxin from Heterometrus laoticus scorpion venom. Toxicon. 2007;49(1):19–29.

    CAS  PubMed  Google Scholar 

  • Upadhyay SK, Eckel-Mahan KL, Mirbolooki MR, Tjong I, Griffey SM, Schmunk G, et al. Selective Kv1.3 channel blocker as therapeutic for obesity and insulin resistance. Proc Natl Acad Sci U S A. 2013;110(24):E2239–48.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vacher H, Romi-Lebrun R, Mourre C, Lebrun B, Kourrich S, Masmejean F, et al. A new class of scorpion toxin binding sites related to an A-type K+ channel: pharmacological characterization and localization in rat brain. FEBS Lett. 2001;501(1):31–6.

    CAS  PubMed  Google Scholar 

  • Vacher H, Alami M, Crest M, Possani LD, Bougis PE, Martin-Eauclaire MF. Expanding the scorpion toxin alpha-KTX 15 family with AmmTX3 from Androctonus mauretanicus. Eur J Biochem. 2002;269(24):6037–41.

    CAS  PubMed  Google Scholar 

  • Vacher H, Prestipino G, Crest M, Martin-Eauclaire MF. Definition of the alpha-KTx15 subfamily. Toxicon. 2004;43(8):887–94.

    CAS  PubMed  Google Scholar 

  • Vandendriessche T, Kopljar I, Jenkins DP, Diego-Garcia E, Abdel-Mottaleb Y, Vermassen E, et al. Purification, molecular cloning and functional characterization of HelaTx1 (Heterometrus laoticus): the first member of a new kappa-KTX subfamily. Biochem Pharmacol. 2012;83(9):1307–17.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Varga Z, Gurrola-Briones G, Papp F, Rodriguez de la Vega RC, Pedraza-Alva G, Tajhya RB, et al. Vm24, a natural immunosuppressive peptide, potently and selectively blocks Kv1.3 potassium channels of human T cells. Mol Pharmacol. 2012;82(3):372–82.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wulff H, Castle NA. Therapeutic potential of KCa3.1 blockers: recent advances and promising trends. Expert Rev Clin Pharmacol. 2010;3(3):385–96.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wulff H, Calabresi PA, Allie R, Yun S, Pennington M, Beeton C, et al. The voltage-gated Kv1.3 K(+) channel in effector memory T cells as new target for MS. J Clin Invest. 2003;111(11):1703–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xu CQ, Brone B, Wicher D, Bozkurt O, Lu WY, Huys I, et al. BmBKTx1, a novel Ca2+-activated K+ channel blocker purified from the Asian scorpion Buthus martensi Karsch. J Biol Chem. 2004;279(33):34562–9.

    CAS  PubMed  Google Scholar 

  • Zachariae U, Schneider R, Velisetty P, Lange A, Seeliger D, Wacker SJ, et al. The molecular mechanism of toxin-induced conformational changes in a potassium channel: relation to C-type inactivation. Structure. 2008;16(5):747–54.

    CAS  PubMed  Google Scholar 

  • Zerrouk H, Laraba-Djebari F, Fremont V, Meki A, Darbon H, Mansuelle P, et al. Characterization of PO1, a new peptide ligand of the apamin-sensitive Ca2+ activated K+ channel. Int J Pept Protein Res. 1996;48(6):514–21.

    CAS  PubMed  Google Scholar 

  • Zhao Q, Chae YK, Markley JL. NMR solution structure of ATTp, an Arabidopsis thaliana trypsin inhibitor. Biochemistry. 2002;41(41):12284–96.

    CAS  PubMed  Google Scholar 

  • Zhu S, Tytgat J. The scorpine family of defensins: gene structure, alternative polyadenylation and fold recognition. Cell Mol Life Sci. 2004;61(14):1751–63.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biophysics and Cell Biology, University of Debrecen, 98. Nagyerdei krt., 4032, Debrecen, Hungary

    Adam Bartok, Gyorgy Panyi & Zoltan Varga

Authors
  1. Adam Bartok
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gyorgy Panyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zoltan Varga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adam Bartok .

Editor information

Editors and Affiliations

  1. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

  2. Departamento de Ciências Fisiológicas -, Universidade de Brasília Laboratório de Toxinologia, Brasilia, Brazil

    Elisabeth Ferroni Schwartz

  3. Universidad Nacional Autonoma de Mexico, Cuernavaca, Morelos, Mexico

    Lourival D. Possani

  4. Laboratoire Ecologie, Systématique et Ev Université Paris-Sud, CNRS, ORSAY Cedex, France

    Ricardo C. Rodríguez de la Vega

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Bartok, A., Panyi, G., Varga, Z. (2014). Potassium Channel-Blocking Peptide Toxins from Scorpion Venom. In: Gopalakrishnakone, P., Ferroni Schwartz, E., Possani, L., Rodríguez de la Vega, R. (eds) Scorpion Venoms. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6647-1_30-1

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-6647-1_30-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-6647-1

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation