Animal toxins influence voltage-gated sodium channel function

Handbook of Experimental Pharmacology

Volumn 221, Issue , 2014, Pages 203-229

  Gilchrist, John ^a   Olivera, Baldomero M ^b   Bosmans, Frank ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF UTAH   (United States)

Author keywords

Animal toxin; Gating modifier; Pore blocker; Sodium channel; Venom

Indexed keywords

BATRACHOTOXIN; BREVETOXIN; CIGUATOXIN; SAXITOXIN; SCORPION VENOM; SEA ANEMONE TOXIN; SNAIL VENOM; SPIDER VENOM; TETRODOTOXIN; TOXIN; VOLTAGE GATED SODIUM CHANNEL; WASP VENOM; SODIUM; SODIUM CHANNEL BLOCKING AGENT;

ARTICLE; BINDING AFFINITY; CHANNEL GATING; CONUS (SNAIL); DRUG DESIGN; DRUG MECHANISM; HUMAN; NONHUMAN; PHYLOGENETIC TREE; PORE REGION; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; ANIMAL; DRUG EFFECT; METABOLISM; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; HUMANS; ION CHANNEL GATING; SIGNAL TRANSDUCTION; SODIUM; SODIUM CHANNEL BLOCKERS; TOXINS, BIOLOGICAL; VOLTAGE-GATED SODIUM CHANNELS;

EID: 84903900359     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/978-3-642-41588-3_10     Document Type: Article

References (201)

1. Abe T, Kawai N, Niwa A (1982) Purification and properties of a presynaptically acting neurotoxin, mandaratoxin, from hornet (Vespa mandarinia). Biochemistry 21(7):1693–1697
2. Agnew WS et al (1978) Purification of the tetrodotoxin-binding component associated with the voltage-sensitive sodium channel from Electrophorus electricus electroplax membranes. Proc Natl Acad Sci U S A 75(6):2606–10
3. Alabi AA et al (2007) Portability of paddle motif function and pharmacology in voltage sensors. Nature 450(7168):370–5
4. Alsen C, Harris J, Tesseraux I (1981) Mechanical and electrophysiological effects of sea anemone (Anemonia sulcata) toxins on rat innervated and denervated skeletal muscle. Br J Pharmacol 74 (1):61–71
5. Ashcroft F (1999) Ion channels and disease, vol 1. Elsevier, Amsterdam, p 481
6. Bagnis R et al (1980) Origins of ciguatera fish poisoning: a new dinoflagellate, Gambierdiscus toxicus Adachi and Fukuyo, definitively involved as a causal agent. Toxicon 18(2):199–208
7. Baldomero MO, Patrice SC, Maren W, Alexander F (2014) Biodiversity of cone snails and other venomous marine gastropods: evolutionary success through neuropharmacology. Annu Rev Anim Biosci 2:487–513
8. Barbier J et al (2004) A d-conotoxin from Conus ermineus venom inhibits inactivation in vertebrate neuronal Na+ channels but not in skeletal and cardiac muscles. J Biol Chem 279:4680–4685
9. Barchi R, Cohen S, Murphy L (1980) Purification from rat sarcolemma of the saxitoxin-binding component of the excitable membrane sodium channel. Proc Natl Acad Sci U S A 77(3):1306–1310
10. Barhanin J et al (1981) Structure-function relationships of sea anemone toxin II from Anemonia sulcata. J Biol Chem 256(11):5764–5769
11. Baron A et al (2013) Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels. Toxicon 75:187–204
12. Benoit E, Legrand A, Dubois J (1986) Effects of ciguatoxin on current and voltage clamped frog myelinated nerve fibre. Toxicon 24(4):357–364
13. Benzinger G et al (1998) A specific interaction between the cardiac sodium channel and site-3 toxin anthopleurin B. J Biol Chem 273(1):80–84
14. Bidard J et al (1984) Ciguatoxin is a novel type of Na+ channel toxin. J Biol Chem 259(13):8353–8357
15. Billen B, Bosmans F, Tytgat J (2008) Animal peptides targeting voltage-activated sodium channels. Curr Pharm Des 14(24):2492–502
16. Bosmans F, Escoubas P, Nicholson GM (2009) Animal toxins: state of the art. In: De Lima ME (ed) Perspectives in health and biotechnology. Editora UFMG
17. Belo Horizonte Bosmans F, Swartz KJ (2010) Targeting voltage sensors in sodium channels with spider toxins. Trends Pharmacol Sci 31(4):175–182
18. Bosmans F et al (2004) The poison Dart frog’s batrachotoxin modulates Nav1.8. FEBS Lett 577 (1–2):245–8
19. Bosmans F et al (2006) Four novel tarantula toxins as selective modulators of voltage-gated sodium channel subtypes. Mol Pharmacol 69(2):419–29
20. Bosmans F, Martin-Eauclaire MF, Swartz KJ (2008) Deconstructing voltage sensor function and pharmacology in sodium channels. Nature 456(7219):202–8
21. Bosmans F et al (2011) Functional properties and toxin pharmacology of a dorsal root ganglion sodium channel viewed through its voltage sensors. J Gen Physiol 138(1):59–72
22. Buczek O et al (2005a) Characterization of D-amino-acid-containing excitatory conotoxins and redefinition of the I-conotoxin superfamily. FEBS J 272(16):4178–88
23. Buczek O, Bulaj G, Olivera BM (2005b) Conotoxins and the posttranslational modification of secreted gene products. CMLS 62(24):3067–79
24. Buczek O et al (2008) I(1)-superfamily conotoxins and prediction of single D-amino acid occurrence. Toxicon 51(2):218–29
25. Bulaj G (2008) Integrating the discovery pipeline for novel compounds targeting ion channels. Curr Opin Chem Biol 12(4):441–7
26. Bulaj G et al (2001) d-Conotoxin structure/function through a cladistic analysis. Biochemistry 40:13201-13208
27. Bulaj G et al (2005) Novel conotoxins from Conus striatus and Conus kinoshitai selectively block TTX-resistant sodium channels. Biochemistry 44:7259–7265
28. Bulaj G et al (2006) Synthetic μO-conotoxin MrVIB blocks TTX-resistant sodium channel Nav1.8 and has a long-lasting analgesic activity. Biochemistry 45:7404–7414
29. Cahalan MD (1975) Modification of sodium channel gating in frog myelinated nerve fibres by Centruroides sculpturatus scorpion venom. J Physiol 244(2):511–34
30. Campos F, Coronas F, Beirão P (2004) Voltage-dependent displacement of the scorpion toxin Ts3 from sodium channels and its implication on the control of inactivation. Br J Pharmacol 142 (7):1115–1122
31. Campos FV et al (2007) beta-Scorpion toxin modifies gating transitions in all four voltage sensors of the sodium channel. J Gen Physiol 130(3):257–68
32. Campos FV et al (2008) Alpha-scorpion toxin impairs a conformational change that leads to fast inactivation of muscle sodium channels. J Gen Physiol 132(2):251–63
33. Capes DL et al (2012) Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor. Proc Natl Acad Sci U S A 109(7):2648–53
34. Catterall W (1975) Activation of the action potential Na+ ionophore of cultured neuroblastoma cells by veratridine and batrachotoxin. J Biol Chem 250(11):4053–4059
35. Catterall WA (1980) Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. Annu Rev Pharmacol Toxicol 20:15–43
36. Catterall WA (2000) From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26(1):13–25
37. Catterall W, Beress L (1978) Sea anemone toxin and scorpion toxin share a common receptor site associated with the action potential sodium ionophore. J Biol Chem 253(20):7393–7396
38. Catterall WA, Goldin AL, Waxman SG (2005) International Union of Pharmacology XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev 57(4):397–409
39. Catterall WA et al (2007) Voltage-gated ion channels and gating modifier toxins. Toxicon 49 (2):124–41
40. Cestèle S et al (1998) Voltage sensor-trapping: enhanced activation of sodium channels by betascorpion toxin bound to the S3-S4 loop in domain II. Neuron 21(4):919–931
41. Cestèle S et al (2006) Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin. J Biol Chem 281(30):21332–21344
42. Cha A et al (1999) Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation. Neuron 22(1):73–87
43. Chanda B, Bezanilla F (2002) Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation. J Gen Physiol 120(5):629–45
44. Chandy KG et al (2004) K+ channels as targets for specific immunomodulation. Trends Pharmacol Sci 25(5):280–9
45. Cooper EC, Tomiko SA, Agnew WS (1987) Reconstituted voltage-sensitive sodium channel from Electrophorus electricus: chemical modifications that alter regulation of ion permeability. Proc Natl Acad Sci U S A 84(17):6282–6
46. Corzo G et al (2007) Solution structure and alanine scan of a spider toxin that affects the activation of mammalian voltage-gated sodium channels. J Biol Chem 282(7):4643–52
47. Couraud F et al (1982) Two types of scorpion receptor sites, one related to the activation, the other to the inactivation of the action potential sodium channel. Toxicon 20(1):9–16
48. Cruz LJ et al (1985) Conus geographus toxins that discriminate between neuronal and muscle sodium channels. J Biol Chem 260:9280–9288
49. Cummins TR et al (1999) A novel persistent tetrodotoxin-resistant sodium current in SNS-null and wild-type small primary sensory neurons. J Neurosci 19(24):RC43
50. Daly NL et al (2004) Structures of muO-conotoxins from Conus marmoreus. I nhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons. J Biol Chem 279(24):25774–82
51. de la Vega R, Vega RC, Possani LD (2005) Overview of scorpion toxins specific for Na+ channels and related peptides: biodiversity, structure-function relationships and evolution. Toxicon 46 (8):831–44
52. Du Y et al (2011) Identification of new batrachotoxin-sensing residues in segment IIIS6 of the sodium channel. J Biol Chem 286(15):13151–60
53. Dumbacher J, Spande T, Daly J (2000) Batrachotoxin alkaloids from passerine birds: a second toxic bird genus (Ifrita kowaldi) from New Guinea. Proc Natl Acad Sci U S A 97(24):12970–12975
54. Dumbacher J et al (2004) Melyrid beetles (Choresine): a putative source for the batrachotoxin alkaloids found in poison-dart frogs and toxic passerine birds. Proc Natl Acad Sci U S A 101 (45):15857–15860
55. Edgerton GB, Blumenthal KM, Hanck DA (2008) Evidence for multiple effects of ProTxII on activation gating in Na(V)1.5. Toxicon 52(3):489–500
56. Ekberg J et al (2006) muO-conotoxin MrVIB selectively blocks Nav1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits. Proc Natl Acad Sci U S A 103(45):17030–5
57. Escoubas P et al (2002) Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies. Mol Pharmacol 62(1):48–57
58. Fainzilber M et al (1995) New sodium channel blocking conotoxins also affect calcium currents in Lymnaea neurons. Biochemistry 34:5364–5371
59. Felix JP et al (2004) Functional assay of voltage-gated sodium channels using membrane potential-sensitive dyes. Assay Drug Dev Technol 2(3):260–8
60. Fiedler B et al (2008) Specificity, affinity and efficacy of iota-conotoxin RXIA, an agonist of voltage-gated sodium channels Na(V)1.2, 1.6 and 1.7. Biochem Pharmacol 75(12):2334–44
61. Fozzard HA, Lipkind GM (2010) The tetrodotoxin binding site is within the outer vestibule of the sodium channel. Marine Drugs 8(2):219–34
62. Furukawa T, Sasaoka T, Hosoya Y (1959) Effects of tetrodotoxin on the neuromuscular junction. Jpn J Physiol 9(2):143–52
63. Gallagher M, Blumenthal K (1994) Importance of the unique cationic residues arginine 12 and lysine 49 in the activity of the cardiotonic polypeptide anthopleurin B. J Biol Chem 269 (1):254–259
64. Gilchrist J, Bosmans F (2012) Animal toxins can alter the function of Nav1.8 and Nav1.9. Toxins 4 (8):620–32
65. Gill S et al (2003) Flux assays in high throughput screening of ion channels in drug discovery. Assay Drug Dev Technol 1(5):709–17
66. Gooley P, Blunt J, Norton R (1984) Conformational heterogeneity in polypeptide cardiac stimulants from sea anemones. FEBS Lett 174(1):15–19
67. Hanck D, Sheets M (2007) Site-3 toxins and cardiac sodium channels. Toxicon 49(2):181–193
68. Hartshorne R, Catterall W (1981) Purification of the saxitoxin receptor of the sodium channel from rat brain. Proc Natl Acad Sci U S A 78(7):4620-4624
69. Hartshorne R et al (1982) The saxitoxin receptor of the sodium channel from rat brain. Evidence for two nonidentical beta subunits. J Biol Chem 257(23):13888–13891
70. Hasson A et al (1993) Alteration of sodium currents by new peptide toxins from the venom of a molluscivorous Conus snail. Eur J Neurosci 5(1):56–64
71. Hille B (1975) The receptor for tetrodotoxin and saxitoxin. A structural hypothesis. Biophys J 15 (6):615–619
72. Hille B (2001) Ion channels of excitable membranes, vol 1, 3rd edn. Sinauer Associates, Sunderland, MA, p 814
73. Hillyard DR et al (1989) A molluscivorous Conus toxin: conserved frameworks in conotoxins. Biochemistry 28(1):358–61
74. Hirama M et al (2001) Total synthesis of ciguatoxin CTX3C. Science (New York, NY) 294 (5548):1904–1907
75. Hodgkin AL, Huxley AF (1952) Propagation of electrical signals along giant nerve fibers. Proc R Soc Lond B Biol Sci 140(899):177–83
76. Holford M et al (2009) Pruning nature: Biodiversity-derived discovery of novel sodium channel blocking conotoxins from Conus bullatus. Toxicon 53(1):90–8
77. Honma T, Shiomi K (2006) Peptide toxins in sea anemones: structural and functional aspects. Marine Biotechnol 8(1):1–10
78. Horn R, Ding S, Gruber HJ (2000) Immobilizing the moving parts of voltage-gated ion channels. J Gen Physiol 116(3):461–76
79. Huang L, Moran N, Ehrenstein G (1982) Batrachotoxin modifies the gating kinetics of sodium channels in internally perfused neuroblastoma cells. Proc Natl Acad Sci U S A 79(6):2082–2085
80. Jiang Y et al (2003) X-ray structure of a voltage-dependent K+ channel. Nature 423(6935):33–41
81. Jimenez EC et al (2003) Novel excitatory Conus peptides define a new conotoxin superfamily. J Neurochem 85(3):610–21
82. Jover E et al (1978) Scorpion toxin: specific binding to rat synaptosomes. Biochem Biophys Res Commun 85(1):377–382
83. Kem W et al (1989) Isolation, characterization, and amino acid sequence of a polypeptide neurotoxin occurring in the sea anemone Stichodactyla helianthus. Biochemistry 28 (8):3483–3489
84. Khera P, Blumenthal K (1996) Importance of highly conserved anionic residues and electrostatic interactions in the activity and structure of the cardiotonic polypeptide anthopleurin B. Biochemistry 35(11):3503–3507
85. Kinoshita E et al (2001) Novel wasp toxin discriminates between neuronal and cardiac sodium channels. Molecular pharmacology 59(6):1457–1463
86. Knapp O, McArthur JR, Adams DJ (2012) Conotoxins targeting neuronal voltage-gated sodium channel subtypes: potential analgesics? Toxins 4(11):1236–60
87. Konno K et al (1998) Isolation and structure of pompilidotoxins, novel peptide neurotoxins in solitary wasp venoms. Biochem Biophys Res Commun 250(3):612–616
88. Konno K et al (2000) Molecular determinants of binding of a wasp toxin (PMTXs) and its analogs in the Na+ channels proteins. Neurosci Lett 285(1):29–32
89. Koppenhofer E, Schmidt H (1968a) Effect of scorpion venom on ionic currents of the node of Ranvier. I. The permeabilities PNa and PK. Pflugers Arch 303(2):133–49
90. Koppenhofer E, Schmidt H (1968b) Effect of scorpion venom on ionic currents of the node of Ranvier. II. Incomplete sodium inactivation. Pflugers Arch 303(2):150–61
91. Kuang Z, Zhang M-M, Gupta K, Gajewiak J, Gulyas J, Balaram P, Rivier JE, Olivera BM, Yoshikami D, Bulaj G, Norton RS (2013) Mammalian neuronal sodium channel blocker μ- conotoxin BuIIIB has a structured N-terminus that influences potency. ACS Chem Biol 8 (6):1344–1351
92. Lee CW et al (2004) Solution structure and functional characterization of SGTx1, a modifier of Kv2.1 channel gating. Biochemistry 43(4):890–7
93. Leffler A et al (2005) Pharmacological properties of neuronal TTX-resistant sodium channels and the role of a critical serine pore residue. Pflugers Archiv 451(3):454–63
94. Legrand AM et al (1989) Isolation and some properties of ciguatoxin. J Appl Phycol 1:183–188
95. Leipold E et al (2005) Molecular interaction of delta-conotoxins with voltage-gated sodium channels. FEBS Lett 579(18):3881–4
96. Leipold E et al (2006) Subtype specificity of scorpion beta-toxin Tz1 interaction with voltagegated sodium channels is determined by the pore loop of domain 3. Mol Pharmacol 70(1):340–347
97. Leipold E et al (2007) μO conotoxins inhibit NaV channels by interfering with their voltage sensors in domain-2. Channels (Austin) 1(4):253–62
98. Leipold E et al (2011) Molecular determinants for the subtype specificity of mu-conotoxin SIIIA targeting neuronal voltage-gated sodium channels. Neuropharmacology 61(1–2):105–11
99. Leipold E, Borges A, Heinemann SH (2012) Scorpion beta-toxin interference with NaV channel voltage sensor gives rise to excitatory and depressant modes. J Gen Physiol 139(4):305–19
100. Lewis R et al (1991) Purification and characterization of ciguatoxins from moray eel (Lycodontis javanicus, Muraenidae). Toxicon 29(9):1115–1127
101. Lewis RJ et al (2007) Isolation and structure-activity of mu-conotoxin TIIIA, a potent inhibitor of tetrodotoxin-sensitive voltage-gated sodium channels. Mol Pharmacol 71(3):676–85
102. Li D et al (2003) Function and solution structure of hainantoxin-I, a novel insect sodium channel inhibitor from the Chinese bird spider Selenocosmia hainana. FEBS Lett 555(3):616–22
103. Liao Z et al (2007) Solution structure of Jingzhaotoxin-III, a peptide toxin inhibiting both Nav1.5 and Kv2.1 channels. Toxicon 50(1):135–43
104. Linford N et al (1998) Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel. Proc Natl Acad Sci U S A 95(23):13947–13952
105. Lipkind G, Fozzard H (1994) A structural model of the tetrodotoxin and saxitoxin binding site of the Na+ channel. Biophys J 66(1):1–13
106. Lipkind GM, Fozzard HA (2008) Voltage-gated Na channel selectivity: the role of the conserved domain III lysine residue. J Gen Physiol 131(6):523–9
107. Llewellyn L, Bell P, Moczydlowski E (1997) Phylogenetic survey of soluble saxitoxin-binding activity in pursuit of the function and molecular evolution of saxiphilin, a relative of transferrin. Proc R Soc 264(1383):891–902
108. Llewellyn L, Doyle J, Negri A (1998) A high-throughput, microtiter plate assay for paralytic shellfish poisons using the saxitoxin-specific receptor, saxiphilin. Anal Biochem 261(1):51–56
109. Lombet A, Bidard J, Lazdunski M (1987) Ciguatoxin and brevetoxins share a common receptor site on the neuronal voltage-dependent Na+ channel. FEBS Lett 219(2):355–359
110. Long SB et al (2007) Atomic structure of a voltage-dependent K+ channel in a lipid membranelike environment. Nature 450(7168):376–82
111. Marcotte P et al (1997) Effects of Tityus serrulatus scorpion toxin gamma on voltage-gated Na+ channels. Circ Res 80(3):363–9
112. Martin-Eauclaire MF, Couraud F (1992) Scorpion neurotoxins: effects and mechanisms. In: Chang LW, Dyer RS (eds) Handk. neurotoxicology. Marcel-Dekker, New York, NY
113. M’Barek S et al (2004) First chemical synthesis of a scorpion alpha-toxin affecting sodium channels: the Aah I toxin of Androctonus australis hector. J Peptide Sci 10(11):666–677
114. McArthur JR et al (2011) Interactions of key charged residues contributing to selective block of neuronal sodium channels by mu-conotoxin KIIIA. Mol Pharmacol 80(4):573–84
115. McCusker EC et al (2012) Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing. Nat Commun 3:1102
116. McIntosh JM et al (1995) A new family of conotoxins that blocks voltage-gated sodium channels. J Biol Chem 270:16796–16802
117. Mebs D (2002) Venomous and poisonous animals: a handbook for biologists, toxicologists and toxinologists, physicians and pharmacists, 1st edn. Medpharm, Lyttelton, New Zealand, p 360
118. Michio M et al (1989) Structures of ciguatoxin and its congener. J Am Chem Soc 111:8289–8931
119. Middleton RE et al (2002) Two tarantula peptides inhibit activation of multiple sodium channels. Biochemistry 41(50):14734–47
120. Milescu M et al (2007) Tarantula toxins interact with voltage sensors within lipid membranes. J Gen Physiol 130(5):497–511
121. Milescu M et al (2009) Interactions between lipids and voltage sensor paddles detected with tarantula toxins. Nat Struct Mol Biol 16(10):1080–1085
122. Miller J, Agnew W, Levinson S (1983) Principal glycopeptide of the tetrodotoxin/saxitoxin binding protein from electrophorus electricus: isolation and partial chemical and physical characterization. Biochemistry 22(2):462–470
123. Moore JW et al (1967) Basis of tetrodotoxin’s selectivity in blockage of squid axons. J Gen Physiol 50(5):1401–11
124. Morabito M, Moczydlowski E (1994) Molecular cloning of bullfrog saxiphilin: a unique relative of the transferrin family that binds saxitoxin. Proc Natl Acad Sci U S A 91(7):2478–2482
125. Narahashi T (1974) Chemicals as tools in the study of excitable membranes. Physiol Rev 54 (4):813–89
126. Narahashi T, Moore JW, Scott WR (1964) Tetrodotoxin blockage of sodium conductance increase in lobster giant axons. J Gen Physiol 47:965–74
127. Narahashi T, Anderson N, Moore J (1967) Comparison of tetrodotoxin and procaine in internally perfused squid giant axons. J Gen Physiol 50(5):1413–1428
128. Nieto FR et al (2012) Tetrodotoxin (TTX) as a therapeutic agent for pain. Marine Drugs 10 (2):281–305
129. Norton R (2009) Structures of sea anemone toxins. Toxicon 54(8):1075–1088
130. Norton RS, Pennington MW, Wulff H (2004) Potassium channel blockade by the sea anemone toxin ShK for the treatment of multiple sclerosis and other autoimmune diseases. Curr Med Chem 11(23):3041–52
131. Nunes KP et al (2013) New insights on arthropod toxins that potentiate erectile function. Toxicon 69:152–9
132. Oliveira J et al (2004) Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels: unexpected contributions from differences in the IV/S3-S4 outer loop. J Biol Chem 279 (32):33323–33335
133. Olivera BM (1997) Conus venom peptides, receptor and ion channel targets and drug design: 50 million years of neuropharmacology (E.E. Just Lecture, 1996). Mol Biol Cell 8:2101–2109
134. Payandeh J et al (2011) The crystal structure of a voltage-gated sodium channel. Nature 475 (7356):353–8
135. Payandeh J et al (2012) Crystal structure of a voltage-gated sodium channel in two potentially inactivated states. Nature 486(7401):135–9
136. Phillips LR et al (2005) Voltage-sensor activation with a tarantula toxin as cargo. Nature 436 (7052):857–60
137. Quandt F, Narahashi T (1982) Modification of single Na+ channels by batrachotoxin. Proc Natl Acad Sci U S A 79(21):6732–6736
138. Richard Benzinger G (1999) G. Tonkovich, and D. Hanck, Augmentation of recovery from inactivation by site-3 Na channel toxins. A single-channel and whole-cell study of persistent currents. J Gen Physiol 113(2):333–346
139. Rogers J et al (1996) Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit. J Biol Chem 271(27):15950–15962
140. Romey G et al (1976) Sea anemone toxin:a tool to study molecular mechanisms of nerve conduction and excitation-secretion coupling. Proc Natl Acad Sci U S A 73(11):4055–4059
141. Ruta V, MacKinnon R (2004) Localization of the voltage-sensor toxin receptor on KvAP. Biochemistry 43(31):10071–9
142. Sahara Y et al (2000) A new class of neurotoxin from wasp venom slows inactivation of sodium current. Eur J Neurosci 12(6):1961–1970
143. Schantz E et al (1975) Letter: The structure of saxitoxin. J Am Chem Soc 97(5):1238
144. Schmalhofer WA et al (2008) ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors. Mol Pharmacol 74(5):1476–84
145. Seibert A et al (2003) Arg-14 loop of site 3 anemone toxins: effects of glycine replacement on toxin affinity. Biochemistry 42(49):14515–14521
146. Sheets MF et al (1999) The Na channel voltage sensor associated with inactivation is localized to the external charged residues of domain IV, S4. Biophys J 77(2):747–57
147. Sheets MF, Kyle JW, Hanck DA (2000) The role of the putative inactivation lid in sodium channel gating current immobilization. J Gen Physiol 115(5):609–20
148. Sherif N, Fozzard H, Hanck D (1992) Dose-dependent modulation of the cardiac sodium channel by sea anemone toxin ATXII. Circul Res 70(2):285–301
149. Shon KJ et al (1994) Delta-conotoxin GmVIA, a novel peptide from the venom of Conus gloriamaris. Biochemistry 33(38):11420–5
150. Shon K et al (1995) Purification, characterization and cloning of the lockjaw peptide from Conus purpurascens venom. Biochemistry 34:4913–4918
151. Shon K (1998) μ-Conotoxin PIIIA, a new peptide for discriminating among tetrodotoxinsensitive Na channel subtypes. J. Neurosci 18:473–4481
152. Silva AO et al (2012) Inhibitory effect of the recombinant Phoneutria nigriventer Tx1 toxin on voltage-gated sodium channels. Biochimie 94(12):2756–63
153. Sivilotti L et al (1997) A single serine residue confers tetrodotoxin insensitivity on the rat sensoryneuron- specific sodium channel SNS. FEBS Lett 409(1):49–52
154. Smith JJ, Blumenthal KM (2007) Site-3 sea anemone toxins: molecular probes of gating mechanisms in voltage-dependent sodium channels. Toxicon 49(2):159–70
155. Smith JJ et al (2005) Differential phospholipid binding by site 3 and site 4 toxins. Implications for structural variability between voltage-sensitive sodium channel domains. J Biol Chem 280 (12):11127–33
156. Smith JJ et al (2007) Molecular interactions of the gating modifier toxin ProTx-II with NaV 1.5: implied existence of a novel toxin binding site coupled to activation. J Biol Chem 282 (17):12687–97
157. Sokolov S et al (2008) Inhibition of sodium channel gating by trapping the domain II voltage sensor with protoxin II. Mol Pharmacol 73(3):1020–8
158. Stroud MR, Hansen SJ, Olson JM (2011) In vivo bio-imaging using chlorotoxin-based conjugates. Curr Pharmaceut Design 17(38):4362–71
159. Sudarslal S et al (2003) Sodium channel modulating activity in a delta-conotoxin from an Indian marine snail. FEBS letters 553(1–2):209–12
160. Swartz KJ (2007) Tarantula toxins interacting with voltage sensors in potassium channels. Toxicon 49(2):213–30
161. Swartz KJ (2008) Sensing voltage across lipid membranes. Nature 456(7224):891–7
162. Swartz KJ, MacKinnon R (1997a) Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites. Neuron 18(4):665–73
163. Swartz KJ, MacKinnon R (1997b) Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels. Neuron 18(4):675–82
164. Teichert RW, et al (2012) Characterization of two neuronal subclasses through constellation pharmacology. In: Proceedings of the National Academy of Sciences. PNAS Early Edition: p. Published ahead of print, July 9
165. Tejedor F, Catterall W (1988) Site of covalent attachment of alpha-scorpion toxin derivatives in domain I of the sodium channel alpha subunit. Proc Natl Acad Sci U S A 85(22):8742–8746
166. Terlau H, Olivera BM (2004) Conus venoms: a rich source of novel ion channel-targeted peptides. Physiol Rev 84(1):41–68
167. Terlau H et al (1991) Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II. FEBS Lett 293(1–2):93–96
168. Terlau H et al (1996) Strategy for rapid immobilization of prey by a fish-hunting cone snail. Nature 381:148–151
169. Thomsen W, Catterall W (1989) Localization of the receptor site for alpha-scorpion toxins by antibody mapping: implications for sodium channel topology. Proc Natl Acad Sci U S A 86 (24):10161–10165
170. Tokuyama T, Daly J, Witkop B (1969) The structure of batrachotoxin, a steroidal alkaloid from the Colombian arrow poison frog, Phyllobates aurotaenia, and partial synthesis of batrachotoxin and its analogs and homologs. J Am Chem Soc 91(14):3931–3938
171. Trainer V, Baden D, Catterall W (1994) Identification of peptide components of the brevetoxin receptor site of rat brain sodium channels. J Biol Chem 269(31):19904–19909
172. Ujihara S et al (2008) Interaction of ladder-shaped polyethers with transmembrane alpha-helix of glycophorin A as evidenced by saturation transfer difference NMR and surface plasmon resonance. Bioorg Med Chem Lett 18(23):6115–8
173. Ulbricht W (1998) Effects of veratridine on sodium currents and fluxes. Rev Physiol Biochem Pharmacol 133:1–54
174. Van Der Haegen A, Peigneur S, Tytgat J (2011) Importance of position 8 in μ-conotoxin KIIIA for voltage-gated sodium channel selectivity. FEBS J 278:3408–3418
175. Vita C et al (1995) Scorpion toxins as natural scaffolds for protein engineering. Proc Natl Acad Sci U S A 92(14):6404–6408
176. Walewska A et al (2008) NMR-based mapping of disulfide bridges in cysteine-rich peptides: application to the mu-conotoxin SxIIIA. J Am Chem Soc 130(43):14280–6
177. Wang S, Wang G (1998) Point mutations in segment I-S6 render voltage-gated Na+ channels resistant to batrachotoxin. Proc Natl Acad Sci U S A 95(5):2653–2658
178. Wang GK, Quan C, Wang SY (1998) Local anesthetic block of batrachotoxin-resistant muscle Na + channels. Mol Pharmacol 54(2):389–96
179. Wang S, Nau C, Wang G (2000) Residues in Na(+) channel D3-S6 segment modulate both batrachotoxin and local anesthetic affinities. Biophys J 79(3):1379–1387
180. Wang M et al (2008) JZTX-IV, a unique acidic sodium channel toxin isolated from the spider Chilobrachys jingzhao. Toxicon 52(8):871–80
181. Wang J et al (2011) Mapping the receptor site for alpha-scorpion toxins on a Na+ channel voltage sensor. Proc Natl Acad Sci U S A 108(37):15426–15431
182. Wasserstrom J et al (1993) Modification of cardiac Na+ channels by batrachotoxin: effects on gating, kinetics, and local anesthetic binding. Biophys J 65(1):386–395
183. West PJ et al (2002) μ-Conotoxin SmIIIA, a potent inhibitor of TTX-resistant sodium channels in amphibian sympathetic and sensory neurons. Biochemistry 41:15388–15393
184. West PJ, Bulaj G, Yoshikami D (2005) Effects of delta-conotoxins PVIA and SVIE on sodium channels in the amphibian sympathetic nervous system. J Neurophysiol 94(6):3916–24
185. Wilson MJ et al (2011) μ-conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve. Proc Natl Acad Sci U S A 108 (25):10302–7
186. Woodward R (1964) The structure of tetrodotoxin. Pure Appl Chem 9:49–74
187. Xiao Y et al (2005) Jingzhaotoxin-I, a novel spider neurotoxin preferentially inhibiting cardiac sodium channel inactivation. J Biol Chem 280(13):12069–76
188. Xiao Y et al (2008) Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to receptor site 4 and trapping the domain ii voltage sensor in the closed configuration. J Biol Chem 283(40):27300–13
189. Xiao Y et al (2010) The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation. Mol Pharmacol 78(6):1124–34
190. Xiao Y et al (2011) Common molecular determinants of tarantula huwentoxin-IV inhibition of Na + channel voltage sensors in domains II and IV. J Biol Chem 286(31):27301–10
191. Xu Y et al (2013) Energetic role of the paddle motif in voltage gating of Shaker K(+) channels. Nat Struct Mol Biol 20(5):574–81
192. Yamaoka K et al (2009) Synthetic ciguatoxins selectively activate Nav1.8-derived chimeric sodium channels expressed in HEK293 cells. J Biol Chem 284(12):7597–7605
193. Yong-Yeng L et al (1981) Isolation and structure of brevetoxin B from the “red tide” dinoflagellate Ptychodiscus brevis (Gymnodinium breve). J Am Chem Soc 103:6773–6776
194. Zhang MM et al (2006) Structural and functional diversities among mu-conotoxins targeting TTX-resistant sodium channels. Biochemistry 45(11):3723–32
195. Zhang MM et al (2007) Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels. J Biol Chem 282 (42):30699–706
196. Zhang MM et al (2009) Synergistic and antagonistic interactions between tetrodotoxin and mu-conotoxin in blocking voltage-gated sodium channels. Channels (Austin) 3(1):32–8
197. Zhang MM et al (2010) Cooccupancy of the outer vestibule of voltage-gated sodium channels by micro-conotoxin KIIIA and saxitoxin or tetrodotoxin. J Neurophysiol 104:88–97
198. Zhang X et al (2012) Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. Nature 486(7401):130–4
199. Zhang MM et al (2013a) Co-expression of Na(V) beta-subunits alters the kinetics of inhibition of voltage-gated sodium channels by pore-blocking mu-conotoxins. Br J Pharmacol 168:1597–1610
200. Zhang MM, Wilson MJ, Gajewiak J, Rivier JE, Bulaj G, Olivera BM, Yoshikami D (2013) Pharmacological fractionation of tetrodotoxin-sensitive sodium currents in rat dorsal root ganglion neurons by μ-conotoxins. Br J Pharmacol 169(1):102–14
201. Zorn S et al. (2006) The muO-conotoxin MrVIA inhibits voltage-gated sodium channels by associating with domain-3. FEBS Lett 580(5):1360–4.