• 1
    Díaz P, D'Suze G, Salazar V, Sevcik C, Shannon JD, Sherman NE & Fox JW (2009) Antibacterial activity of six novel peptides from Tityus discrepans scorpion venom. A fluorescent probe study of microbial membrane Na+ permeability changes. Toxicon 54, 802817.
  • 2
    Lambert P, Kuroda H, Chino N, Watanabe TX, Kimura T & Sakakibara S (1990) Solution synthesis of charybdotoxin (ChTX), a K+ channel blocker. Biochem Biophys Res Commun 170, 684690.
  • 3
    Housset D, Habersetzer-Rochat C, Astier JP & Fontecilla-Camps JC (1994) Crystal structure of toxin II from the scorpion Androctonus australis Hector refined at 1.3 Å resolution . J Mol Biol 238, 88103.
  • 4
    Lippens G, Najib J, Wodak SJ & Tartar A (1995) NMR sequential assignments and solution structure of chlorotoxin, a small scorpion toxin that blocks chloride channels. Biochemistry 34, 1321.
  • 5
    Mouhat S, Jouirou B, Mosbah A, de Waard M & Sabatier JM (2004) Diversity of folds in animal toxins acting on ion channels. Biochem J 378, 717726.
  • 6
    Ali SA, Wang B, Alam M, Beck A, Stoeva S, Voelter W, Abbasi A & Duszenko M (2006) Structure–activity relationship of an α-toxin Bs-Tx28 from scorpion (Buthus sindicus) venom suggests a new α-toxin subfamily. Arch Biochem Biophys 445, 8194.
  • 7
    Rodríguez de la Vega RC & Possani LD (2007) Novel paradigms on scorpion toxins that affects the activating mechanism of sodium channels. Toxicon 49, 171180.
  • 8
    Martin-Eauclaire MF & Couraud F (1995) Scorpion neurotoxins: effects and mechanisms. In Handbook of Neurotoxicology (Chang LW & Dyer RS, eds), pp. 683716. Marcel Dekker, New York.
  • 9
    Gordon D, Savarin P, Gurevitz M & Zinn-Justin S (1998) Functional anatomy of scorpion toxins affecting sodium channels. J Toxicol Toxin Rev 17, 131159.
  • 10
    Possani LD, Becerril B, Delepierre M & Tytgat J (1999) Scorpion toxins specific for Na+ channels. Eur J Biochem 264, 287300.
  • 11
    Zuo XP & Ji YH (2004) Molecular mechanism of scorpion neurotoxins acting on sodium channels. Mol Neurobiol 30, 265278.
  • 12
    Froy O & Gurevitz M (2003) New insight on scorpion divergence inferred from comparative analysis of toxin structure, pharmacology and distribution. Toxicon 42, 549555.
  • 13
    Zhu S, Bosmans F & Tytgat J (2004) Adaptive evolution of scorpion sodium channel toxins. J Mol Evol 58, 145153.
  • 14
    Bosmans F & Tytgat J (2007) Voltage-gated sodium channel modulation by scorpion α-toxins. Toxicon 49, 142158.
  • 15
    Catterall WA (1995) Structure and function of voltage-gated ion channels. Annu Rev Biochem 64, 493531.
  • 16
    Gordon D (1997) Sodium channels as targets for neurotoxins: mode of action and interaction of neurotoxins with receptor sites on sodium channels. In Toxins and Signal Transduction (Gutman Y & Lazarowici P, eds), pp. 119149. Harwood Academic Publishers, Amsterdam, Netherlands.
  • 17
    Catterall WA, Cestele S, Yarov-Yarovoy V, Yu FH, Konoki K & Scheuer T (2007) Voltage-gated ion channels and gating modifier toxins. Toxicon 49, 124141.
  • 18
    Cèstele S, Qu Y, Rogers JC, Rochat H, Scheuer T & Catterall WA (1998) Voltage sensor-trapping: enhanced activation of sodium channels by β-scorpion toxin bound to the S3–S4 loop in domain II. Neuron 21, 919931.
  • 19
    Borges A, Alfonzo MJ, García CC, Winand NJ, Leipold E & Heinemann SH (2004) Isolation, molecular cloning and functional characterization of a novel β-toxin from the Venezuelan scorpion, Tityus zulianus. Toxicon 43, 671684.
  • 20
    Leipold E, Hansel A, Borges A & Heinemann SH (2006) Subtype specificity of scorpion β-toxin tz1 interaction with voltage-gated sodium channels is determined by the pore loop of domain 3. Mol Pharmacol 70, 340347.
  • 21
    Vandendriessche T, Olamendi-Portugal T, Zamudio FZ, Possani LD & Tytgat J (2010) Isolation and characterization of two novel scorpion toxins: the alpha-toxin-like CeII8, specific for NaV1.7 channels and the classical anti-mammalian CeII9, specific for NaV1.4 channels. Toxicon 56, 613623.
  • 22
    Denac H, Mevissen M & Scholtysik G (2000) Structure, function and pharmacology of voltage-gated sodium channels. Naun-Schmied Arch Pharmacol 362, 453479.
  • 23
    Goldin AL (2001) Resurgence of sodium channel research. Annu Rev Physiol 63, 871894.
  • 24
    Cestele S, Scheuer T, Mantegazza M, Rochat H & Catterall WA (2001) Neutralization of gating charges in domain II of the sodium channel a subunit enhances voltage-sensor trapping by a β-scorpion toxin. J Gen Physiol 118, 291301.
  • 25
    Leipold E, Borges A & Heinemann SH (2012) Scorpion β-toxin interference with NaV channel voltage sensor gives rise to excitatory and depressant modes. J Gen Physiol 139, 305319.
  • 26
    Sternberg D, Maisonobe T, Jurkat-Rott K, Nicole S, Launay E, Chauveau D, Tabti N, Lehmann-Horn F & Hainque B (2001) Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. Brain 124, 10911099.
  • 27
    Li YJ, Tan ZY & Ji YH (2000) The binding of BmK IT2, a depressant insect-selective scorpion toxin on mammal and insect sodium channels. Neurosci Res 38, 257264.
  • 28
    Wang CY, Tan ZY, Chen B, Zhao ZQ & Ji YH (2000) Antihyperalgesia effect of BmK IT2, a depressant insect-selective scorpion toxin in rat by peripheral administration. Brain Res Bull 53, 335338.
  • 29
    Tan ZY, Xiao H, Mao X, Wang CY, Zhao ZQ & Ji YH (2001) The inhibitory effects of BmK IT2, a scorpion neurotoxin on rat nociceptive flexion reflex and a possible mechanism for modulating voltage-gated Na+ channels. Neuropharmacology 40, 352357.
  • 30
    Zhang XY, Bai ZT, Chai ZF, Zhang JW, Liu Y & Ji YH (2003) Suppressive effects of BmK IT2 on nociceptive behavior and c-Fos expression in spinal cord induced by formalin. J Neurosci Res 74, 167173.
  • 31
    Bai ZT, Liu T, Pang XY, Chai ZF & Ji YH (2007) Suppression by intrathecal BmK IT2 on rat spontaneous pain behaviors and spinal c-Fos expression induced by formalin. Brain Res Bull 73, 248253.
  • 32
    Massensini AR, Suckling J, Brammer MJ, Moraes-Santos T, Gomez MV & Romano-Silva MA (2002) Tracking sodium channels in live cells: confocal imaging using fluorescently labeled toxins. J Neurosci Methods 116, 189196.
  • 33
    Tsushima RG, Borges A & Backx PH (1999) Inactivated state dependence of sodium channel modulation by beta-scorpion toxin. Pflüg Arch 437, 661668.
  • 34
    D'Suze G, Schwartz EF, García-Gomez BI, Sevcik C & Possani LD (2009) Molecular cloning and nucleotide sequence analysis of genes from a cDNA library of the scorpion Tityus discrepans. Biochimie 91, 10101019.
  • 35
    Borges A, García CC, Lugo E, Alfonzo MJ, Jowers MJ & op den Camp HJ (2006) Diversity of long-chain toxins in Tityus zulianus and Tityus discrepans venoms (Scorpiones, Buthidae): molecular, immunological, and mass spectral analyses. Comp Biochem Physiol C Toxicol Pharmacol 142, 240252.
  • 36
    Froy O, Sagiv T, Poreh M, Urbach D, Zilberberg N & Gurevitz M (1999) Dynamic diversification from a putative common ancestor of scorpion toxins affecting sodium, potassium and chloride channels. J Mol Evol 48, 187196.
  • 37
    Cohen L, Karbat I, Gilles N, Froy O, Corzo G, Angelovici R, Gordon D & Gurevitz M (2004) Dissection of the functional surface of an anti-insect excitatory toxin illuminates a putative ‘hot spot’ common to all scorpion β-toxins affecting Na+ channels. J Biol Chem 279, 82068211.
  • 38
    Cohen L, Karbat I, Gilles N, Ilan N, Benveniste N, Gordon D & Gurevitz M (2005) Common features in the functional surface of scorpion β-toxins and elements that confer specificity for insect and mammalian voltage-gated sodium channels. J Biol Chem 280, 50455053.
  • 39
    Alonso M & Finn EJ (1967) Fundamental University Physics, Vol. 1. Addison-Wesley, Reading, MA.
  • 40
    Sevcik C (1982) Temperature dependence of tetrodotoxin effect in squid giant axons. J Physiol 325, 187194.
  • 41
    Loret EP, Martin-Eauclaire MF, Mansuelle P, Sampieri F, Granier C & Rochat H (1991) An anti-insect toxin purified from the scorpion Androctonus australis Hector also acts on the α- and β-sites of the mammalian sodium channel: sequence and circular dichroism study. Biochemistry 30, 633640.
  • 42
    Gordon D, Ilan N, Zilberberg N, Gilles N, Urbach D, Cohen L, Karbat I, Froy O, Gaathon A, Kallen RG et al. (2003) An ‘Old World’ scorpion β toxin that recognizes both insect and mammalian sodium channels. Eur J Biochem 270, 26632670.
  • 43
    Bosmans F, Martin-Eauclaire MF & Tytgat J (2005) The depressant scorpion neurotoxin LqqIT2 selectively modulates the insect voltage-gated sodium channel. Toxicon 45, 501507.
  • 44
    Cologna CT, Peigneur S, Rustiguel JK, Nonato MC, Tytgat J & Arantes EC (2012) Investigation of the relationship between the structure and function of Ts2, a neurotoxin from Tityus serrulatus venom. FEBS J 279, 14951504.
  • 45
    Nassar MA, Stirling LC, Forlani G, Baker MD, Matthews EA, Dickenson AH & Wood JN (2004) Nociceptor-specific gene deletion reveals a major role for NaV1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci USA 101, 1270612711.
  • 46
    Diss JK, Stewart D, Pani F, Foster CS, Walker MM, Patel A & Djamgoz MB (2005) A potential novel marker for human prostate cancer: voltage-gated sodium channel expression in vivo. Prost Cancer Prostatic Dis 8, 266273.
  • 47
    Maertens C, Cuypers E, Amininasab M, Jalali A, Vatanpour H & Tytgat J (2006) Potent modulation of the voltage-gated sodium channel NaV1.7 by OD1, a toxin from the scorpion Odonthobuthus doriae. Mol Pharmacol 70, 405414.
  • 48
    Koishi R, Xu H, Ren D, Navarro B, Spiller BW, Shi Q & Clapham DE (2004) A superfamily of voltage-gated sodium channels in bacteria. J Biol Chem 279, 95329538.
  • 49
    Martinac B, Saimi Y & Kung C (2008) Ion channels in microbes. Physiol Rev 88, 14491490.
  • 50
    D'Suze G, Sevcik C & Ramos M (1995) Presence of curarizing polypeptides and a pancreatitisinducing fraction without muscarinic effects in the venom of the Venezuelan scorpion Tityus discrepans (Karsch). Toxicon 33, 333345.
  • 51
    Moerman L, Bosteels S, Noppe W, Willems J, Clynen E, Schoofs L, Thevissen K, Tytgat J, van Eldere J, van der Walt J et al. (2002) Antibacterial and antifungal properties of α-helical, cationic peptides in the venom of scorpions from southern Africa. Eur J Biochem 269, 47994810.
  • 52
    Altschul SF, Thomas L, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W & Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25, 33893402.
  • 53
    Pinheiro CB, Marangoni S, Toyama MH & Polikarpov I (2003) Structural analysis of Tityus serrulatus Ts1 neurotoxin at atomic resolution: insights into interactions with Na+ channels. Acta Crystallogr Sect D 59, 405415.
  • 54
    Guex N & Peitsch MC (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modelling. Electrophoresis 18, 27142723.
  • 55
    Schwede T, Kopp J, Guex N & Peitsch MC (2003) SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Res 31, 33813385.
  • 56
    Arnold K, Bordoli L, Kopp J & Schwede T (2006) The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22, 195201.
  • 57
    Chothia C & Lesk AM (1986) The relation between the divergence of sequence and structure in proteins. EMBO J 5, 823836.
  • 58
    Sander C & Schneider R (1991) Database of homology-derived protein structures and the structural meaning of sequence alignment. Proteins 9, 5668.
  • 59
    Rost B (1999) Twilight zone of protein sequence alignments. Protein Eng 12, 8594.
  • 60
    Ceroni A, Passerini A, Vullo A & Frasconi P (2006) DISULFIND: a disulfide bonding state and cysteine connectivity prediction server. Nucleic Acids Res 34, W177W181.
  • 61
    Krieger E (2004) The Last Mile of the Protein Folding Problem. A Pilgrim's Staff and Skid-proof Boots. PhD Thesis, Center for Molecular and Biomolecular Informatics (CMBI), Radboud University Nijmegen, The Netherlands, September.
  • 62
    Liman ER, Tytgat J & Hess P (1992) Subunit stoichiometry of a mammalian K2+ channel determined by construction of multimeric cDNAs. Neuron 9, 861871.