Venom peptides as a rich source of Cav2.2 channel blockers

Toxins

Volumn 5, Issue 2, 2013, Pages 286-314

  Sousa, Silmara R ^a   Vetter, Irina ^a   Lewis, Richard J ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

conotoxins; Cav2.2; Neurotransmitter; Nociception; Venom peptides; Voltage gated calcium channels

Indexed keywords

CALCIUM CHANNEL BLOCKING AGENT; GABAPENTIN; OMEGA AGATOXIN; OMEGA CONOTOXIN; OMEGA CONOTOXIN CVID; OMEGA CONOTOXIN MVIIA; OMEGA SEGESTRITOXIN; OMEGA THERAPHOTOXIN; PREGABALIN; SCORPION VENOM; SNAIL VENOM; SNAKE VENOM; TOXIN; UNCLASSIFIED DRUG; VOLTAGE GATED CALCIUM CHANNEL; VOLTAGE GATED CALCIUM CHANNEL CAV2.2;

ALTERNATIVE RNA SPLICING; AMINO ACID SEQUENCE; BINDING AFFINITY; BINDING SITE; CALCIUM CURRENT; CANCER PAIN; CHANNEL GATING; CHRONIC PAIN; DRUG MECHANISM; ELECTROPHYSIOLOGY; HIGH THROUGHPUT SCREENING; HUMAN; NEUROPATHIC PAIN; NOCICEPTION; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; SYNAPTIC TRANSMISSION; UPREGULATION;

ANIMALS; CALCIUM CHANNEL BLOCKERS; CALCIUM CHANNELS, N-TYPE; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; PEPTIDES; VENOMS;

EID: 84873565492     PISSN: 20726651     EISSN: None     Source Type: Journal    
DOI: 10.3390/toxins5020286     Document Type: Review

References (149)

1. Lewis, R.J.; Garcia, M.L. Therapeutic potential of venom peptides. Nat. Rev. Drug Discov. 2003, 2, 790-802.
2. Gomez, M.V.; Kalapothakis, E.; Guatimosim, C.; Prado, M.A. Phoneutria nigriventer venom: A cocktail of toxins that affect ion channels. Cell Mol. Neurobiol. 2002, 22, 579-588.
3. Klint, J.K.; Senff, S.; Rupasinghe, D.B.; Er, S.Y.; Herzig, V.; Nicholson, G.M.; King, G.F., Spider-venom peptides that target voltage-gated sodium channels: Pharmacological tools and potential therapeutic leads. Toxicon 2012, 60, 478-491.
4. Herzig, V.; Wood, D.L.; Newell, F.; Chaumeil, P.A.; Kaas, Q.; Binford, G.J.; Nicholson, G.M.; Gorse, D.; King, G.F. Arachnoserver 2.0, an updated online resource for spider toxin sequences and structures. Nucleic Acids Res. 2011, 39, D653-D657.
5. Arachnoserver 2.0. Available online: www.arachnoserver.org (accessed on 12 December 2012).
6. Adams, M.E.; Bindokas, V.P.; Hasegawa, L.; Venema, V.J. Omega-agatoxins: Novel calcium channel antagonists of two subtypes from funnel web spider (agelenopsis aperta) venom. J. Biol. Chem. 1990, 265, 861-867.
7. Dos Santos, R.G.; Van Renterghem, C.; Martin-Moutot, N.; Mansuelle, P.; Cordeiro, M.N.; Diniz, C.R.; Mori, Y.; De Lima, M.E.; Seagar, M. Phoneutria nigriventer ω-phonetoxin iia blocks the cav2 family of calcium channels and interacts with ω-conotoxin-binding sites. J. Biol. Chem. 2002, 277, 13856-13862.
8. Lewis, R.J.; Nielsen, K.J.; Craik, D.J.; Loughnan, M.L.; Adams, D.A.; Sharpe, I.A.; Luchian, T.; Adams, D.J.; Bond, T.; Thomas, L. Novel ω-conotoxins from conus catus discriminate among neuronal calcium channel subtypes. J. Biol. Chem. 2000, 275, 35335-35344.
9. Lewis, R.J.; Dutertre, S.; Vetter, I.; Christie, M.J. Conus venom peptide pharmacology. Pharmacol. Rev. 2012, 64, 259-298.
10. Abbott, J.R.; Litzinger, M.J. Different ω-conotoxins mark the development of swiss webster mouse cortex suggesting N-type voltage sensitive calcium channel subtypes. Int. J. Dev. Neurosci. 1994, 12, 43-47.
11. Ellinor, P.T.; Zhang, J.F.; Horne, W.A.; Tsien, R.W. Structural determinants of the blockade of N-type calcium channels by a peptide neurotoxin. Nature 1994, 372, 272-275.
12. Wagner, J.; Snowman, A.; Biswas, A.; Olivera, B.; Snyder, S. Ω-conotoxin gvia binding to a high affinity receptor in brain: Characterization, calcium sensitivity and solubilization. J. Neurosci. 1988, 9, 3354-3359.
13. Olivera, B.M.; Cruz, L.J.; de Santos, V.; LeCheminant, G.W.; Griffin, D.; Zeikus, R.; McIntosh, J.M.; Galyean, R.; Varga, J.; Gray, W.R. Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using ω-conotoxin from conus magus venom. Biochemistry 1987, 26, 2086-2090.
14. Catterall, W.A. Voltage-gated calcium channels. Cold Spring Harb. Perspect. Biol. 2011, 3, doi:10.1101/cshperspect
15. Miljanich, G.P. Ziconotide: Neuronal calcium channel blocker for treating severe chronic pain. Curr. Med. Chem. 2004, 11, 3029-3040.
16. Berecki, G.; Motin, L.; Haythornthwaite, A.; Vink, S.; Bansal, P.; Drinkwater, R.; Wang, C.I.; Moretta, M.; Lewis, R.J.; Alewood, P.F.; et al. Analgesic ω-conotoxins cvie and cvif selectively and voltage-dependently block recombinant and native N-type calcium channels. Mol. Pharmacol. 2010, 77, 139-148.
17. Terlau, H.; Olivera, B.M. Conus venoms: A rich source of novel ion channel-targeted peptides. Physiol. Rev. 2004, 84, 41-68.
18. Wermeling, D.P. Ziconotide, an intrathecally administered N-type calcium channel antagonist for the treatment of chronic pain. Pharmacotherapy 2005, 25, 1084-1094.
19. Alicino, I.; Giglio, M.; Manca, F.; Bruno, F.; Puntillo, F., Intrathecal combination of ziconotide and morphine for refractory cancer pain: A rapidly acting and effective choice. Pain 2012, 153, 245-249.
20. Catterall, W.A.; Perez-Reyes, E.; Snutch, T.P.; Striessnig, J. International union of pharmacology. Xlviii. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol. Rev. 2005, 57, 411-425.
21. Williams, M.E.; Brust, P.F.; Feldman, D.H.; Patthi, S.; Simerson, S.; Maroufi, A.; McCue, A.F.; Velicelebi, G.; Ellis, S.B.; Harpold, M.M. Structure and functional expression of an ω-conotoxinsensitive human N-type calcium channel. Science 1992, 257, 389-395.
22. Catterall, W.A. Structure and regulation of voltage-gated ca2+ channels. Annu. Rev. Cell Dev. Biol. 2000, 16, 521-555.
23. Yu, F.H.; Catterall, W.A. The vgl-chanome: A protein superfamily specialized for electrical signaling and ionic homeostasis. Sci. STKE 2004, 2004, doi:10.1126/stke.2532004
24. Payandeh, J.; Scheuer, T.; Zheng, N.; Catterall, W.A. The crystal structure of a voltage-gated sodium channel. Nature 2011, 475, 353-358.
25. Payandeh, J.; Gamal El-Din, T.M.; Scheuer, T.; Zheng, N.; Catterall, W.A. Crystal structure of a voltage-gated sodium channel in two potentially inactivated states. Nature 2012, 486, 135-139.
26. Lipscombe, D.; Pan, J.Q.; Gray, A.C. Functional diversity in neuronal voltage-gated calcium channels by alternative splicing of ca(v)α1. Mol. Neurobiol. 2002, 26, 21-44.
27. Lin, Z.; Haus, S.; Edgerton, J.; Lipscombe, D. Identification of functionally distinct isoforms of the N-type ca2+ channel in rat sympathetic ganglia and brain. Neuron 1997, 18, 153-166.
28. Bell, T.J.; Thaler, C.; Castiglioni, A.J.; Helton, T.D.; Lipscombe, D. Cell-specific alternative splicing increases calcium channel current density in the pain pathway. Neuron 2004, 41, 127-138.
29. Lipscombe, D.; Raingo, J. Alternative splicing matters: N-type calcium channels in nociceptors. Channels (Austin) 2007, 1, 225-227.
30. Zamponi, G.W.; McCleskey, E.W. Splicing it up: A variant of the N-type calcium channel specific for pain. Neuron 2004, 41, 3-4.
31. Kaneko, S.; Cooper, C.B.; Nishioka, N.; Yamasaki, H.; Suzuki, A.; Jarvis, S.E.; Akaike, A.; Satoh, M.; Zamponi, G.W., Identification and characterization of novel human ca(v)2.2 (α1b) calcium channel variants lacking the synaptic protein interaction site. J. Neurosci. 2002, 22, 82-92.
32. McDonough, S.I.; Boland, L.M.; Mintz, I.M.; Bean, B.P., Interactions among toxins that inhibit N-type and P-type calcium channels. J. Gen. Physiol. 2002, 119, 313-328.
33. 2+ channels. J. Neurosci. 1997, 17, 3002-3013.
34. Feng, Z.P.; Hamid, J.; Doering, C.; Bosey, G.M.; Snutch, T.P.; Zamponi, G.W., Residue gly1326 of the N-type calcium channel α1b subunit controls reversibility of ω-conotoxin gvia and mviia block. J. Biol. Chem. 2001, 276, 15728-15735.
35. v2.2) calcium channels. J. Biol. Chem. 2004, 279, 34705-34714.
36. Dolphin, A.; Wyatt, C.; Richards, J.; Beattie, R.; Craig, P.; Lee, J.H.; Cribbs, L.; Volsen, S.; Perez-Reyes, E., The effect of α2δ and other accessory subunits on expression and properties of the calcium channel α1g., J. Physiol. 1999, 519, 35-45.
37. Birnbaumer, L.; Qin, N.; Olcese, R.; Tareilus, E.; Platano, D.; Costantin, J.; Stefani, E., Structures and functions of calcium channel β subunits. J. Bioenerg. Biomembr. 1998, 30, 357-375.
38. Takahashi, M.; Seagar, M.J.; Jones, J.F.; Reber, B.F.; Catterall, W.A. Subunit structure of dihydropyridine-sensitive calcium channels from skeletal muscle. Proc. Natl. Acad. Sci. USA 1987, 84, 5478-5482.
39. Arikkath, J.; Campbell, K.P. Auxiliary subunits: Essential components of the voltage-gated calcium channel complex. Curr. Opin. Neurobiol. 2003, 13, 298-307.
40. Dolphin, A.C., Calcium channel diversity: Multiple roles of calcium channel subunits. Curr. Opin. Neurobiol. 2009, 19, 237-244.
41. Davies, A.; Hendrich, J.; Van Minh, A.T.; Wratten, J.; Douglas, L.; Dolphin, A.C. Functional biology of the α2δ subunits of voltage-gated calcium channels. Trends. Pharmacol. Sci. 2007, 28, 220-228.
42. Cole, R.L.; Lechner, S.M.; Williams, M.E.; Prodanovich, P.; Bleicher, L.; Varney, M.A.; Gu, G., Differential distribution of voltage-gated calcium channel α2δ delta (alpha2delta) subunit mrna-containing cells in the rat central nervous system and the dorsal root ganglia. J. Comp. Neurol. 2005, 491, 246-269.
43. 2δ calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats. J. Neurosci. 2001, 21, 1868-1875.
44. Luo, Z.; Calcutt, N.; Higuera, E.; Valder, C.; Song, Y.H.; Svensson, C.; Myers, R. Injury type-specific calcium channel α2δ/1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. J. Pharmacol. Exp. Ther. 2002, 303, 1199-1205.
45. Finnerup, N.B.; Sindrup, S.H.; Jensen, T.S. Chronic neuropathic pain: Mechanisms, drug targets and measurement. Fundam. Clin. Pharmacol. 2007, 21, 129-136.
46. 2δ ligand gabapentin. Proc. Natl. Acad. Sci. USA 2008, 105, 3628-3633.
47. 2δ Subunits in Epilepsy and as Targets for Antiepileptic Drugs. In Jasper's Basic Mechanisms Epilepsies, 4th ed; Noebels, J.L., Avoli, M., Rogawski, M.A., Olsen, R.W., Delgado-Escueta, A.V., Eds. Oxford University Press: Bethesda, Maryland, MD, USA, 2012.
48. Taylor, C.P.; Angelotti, T.; Fauman, E. Pharmacology and mechanism of action of pregabalin: The calcium channel α2/δ (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy. Res. 2007, 73, 137-150.
49. 2δ/1 is a neuronal thrombospondin receptor responsible for excitatory cns synaptogenesis. Cell 2009, 139, 380-392.
50. Pragnell, M.; De Waard, M.; Mori, Y.; Tanabe, T.; Snutch, T.P.; Campbell, K.P. Calcium channel β-subunit binds to a conserved motif in the i-ii cytoplasmic linker of the α1-subunit. Nature 1994, 368, 67-70.
51. 2+ channel regulation by a conserved β subunit domain. Neuron 1994, 13, 495-503.
52. 2+ channel alpha1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit. Neuron 2000, 25, 177-190.
53. 2+ channels. Physiol. Rev. 2010, 90, 1461-1506.
54. 2+ channels. FEBS Lett. 2005, 579, 3907-3912.
55. Altier, C.; Garcia-Caballero, A.; Simms, B.; Walcher, J.; Tedford, H.; Hermosilla, G.; Zamponi, G. The cav β subunit prevents RFT2-mediated ubiquitination and proteasomal degradation l-type calcium channels via the derlin-1/p97 erad protein complex. Nat. Neurosci. 2011, 14, 173-180.
56. Cornet, V.; Bichet, D.; Sandoz, G.; Marty, I.; Brocard, J.; Bourinet, E.; Mori, Y.; Villaz, M.; De Waard, M. Multiple determinants in voltage-dependent p/q calcium channels control their retention in the endoplasmic reticulum. Eur. J. Neurosci. 2002, 16, 883-895.
57. Flucher, B.E.; Kasielke, N.; Grabner, M. The triad targeting signal of the skeletal muscle calcium channel is localized in the cooh terminus of the alpha(1s) subunit. J. Cell Biol. 2000, 151, 467-478.
58. 2+ ions. J. Biol. Chem. 2005, 280, 12474-12485.
59. v2.2 channels by reducing their proteasomal degradation. J. Biol. Chem. 2011, 286, 9598-9611.
60. 2+-channel γ subunit. Nat. Genet. 1998, 19, 340-347.
61. 2+ channels. J. Biol. Chem. 2001, 276, 32917-32924.
62. Yang, L.; Katchman, A.; Morrow, J.P.; Doshi, D.; Marx, S.O. Cardiac l-type calcium channel (Cav1.2) associates with γ subunits. FASEB J. 2011, 25, 928-936.
63. v3.1) calcium current. J. Mol. Cell. Cardiol. 2004, 37, 1147-1158.
64. Sandoval, A.; Arikkath, J.; Monjaraz, E.; Campbell, K.P.; Felix, R. Γ1-dependent down-regulation of recombinant voltage-gated Ca2+ channels. Cell. Mol. Neurobiol. 2007, 27, 901-908.
65. Wallace, M.S.; Rauck, R.L.; Deer, T. Ziconotide combination intrathecal therapy: Rationale and evidence. Clin. J. Pain 2010, 26, 635-644.
66. 2+ channels in the rat spinal cord following chronic constrictive nerve injury. Exp. Brain Res. 2002, 147, 456-463.
67. Zamponi, G.W.; Lewis, R.J.; Todorovic, S.M.; Arneric, S.P.; Snutch, T.P. Role of voltage-gated calcium channels in ascending pain pathways. Brain Res. Rev. 2009, 60, 84-89.
68. Krarup, C. An update on electrophysiological studies in neuropathy. Curr. Opin. Neurol. 2003, 16, 603-612.
69. 2+ channel. EMBO J. 2001, 20, 2349-2356.
70. 2+) channels. Neuroreport 2001, 12, 2423-2427.
71. Zamponi, G.W.; Snutch, T.P. Modulation of voltage-dependent calcium channels by g proteins. Curr. Opin. Neurobiol. 1998, 8, 351-356.
72. 2δ/1 subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. J. Neurosci. 2004, 24, 8494-8499.
73. 1 subunit mediates spinal hyperexcitability in pain modulation. Pain 2006, 125, 20-34.
74. Jain, K.K., An evaluation of intrathecal ziconotide for the treatment of chronic pain. Expert. Opin. Investig. Drugs 2000, 9, 2403-2410.
75. Staats, P.S.; Yearwood, T.; Charapata, S.G.; Presley, R.W.; Wallace, M.S.; Byas-Smith, M.; Fisher, R.; Bryce, D.A.; Mangieri, E.A.; Luther, R.R.; et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or aids: A randomized controlled trial. JAMA 2004, 291, 63-70.
76. Olivera, B.M.; Gray, W.R.; Zeikus, R.; McIntosh, J.M.; Varga, J.; Rivier, J.; de Santos, V.; Cruz, L.J. Peptide neurotoxins from fish-hunting cone snails. Science 1985, 230, 1338-1343.
77. Skalicky, J.J.; Metzler, W.J.; Ciesla, D.J.; Galdes, A.; Pardi, A. Solution structure of the calcium channel antagonist omega-conotoxin gvia. Protein. Sci. 1993, 2, 1591-1603.
78. Norton, R.S.; Pallaghy, P.K. The cystine knot structure of ion channel toxins and related polypeptides. Toxicon 1998, 36, 1573-1583.
79. Olivera, B.M., Conus peptides: Biodiversity-based discovery and exogenomics. J. Biol. Chem. 2006, 281, 31173-31177.
80. Jakubowski, J.A.; Kelley, W.P.; Sweedler, J.V. Screening for post-translational modifications in conotoxins using liquid chromatography/mass spectrometry: An important component of conotoxin discovery., Toxicon 2006, 47, 688-699.
81. Nielsen, K.J.; Adams, D.; Thomas, L.; Bond, T.; Alewood, P.F.; Craik, D.J.; Lewis, R.J. Structure-activity relationships of ω-conotoxins mviia, mviic and 14 loop splice hybrids at n and p/q-type calcium channels. J. Mol. Biol. 1999, 289, 1405-1421.
82. Favreau, P.; Gilles, N.; Lamthanh, H.; Bournaud, R.; Shimahara, T.; Bouet, F.; Laboute, P.; Letourneux, Y.; Menez, A.; Molgo, J.; et al. A new ω-conotoxin that targets N-type voltagesensitive calcium channels with unusual specificity. Biochemistry 2001, 40, 14567-14575.
83. 2+ channels. Mol. Pain 2010, 6, 97.
84. Olivera, B.M.; McIntosh, J.M.; Cruz, L.J.; Luque, F.A.; Gray, W.R. Purification and sequence of a presynaptic peptide toxin from conus geographus venom. Biochemistry 1984, 23, 5087-5090.
85. Sato, K.; Park, N.G.; Kohno, T.; Maeda, T.; Kim, J.I.; Kato, R.; Takahashi, M. Role of basic residues for the binding of ω-conotoxin gvia to N-type calcium channels. Biochem. Biophys. Res. Commun. 1993, 194, 1292-1296.
86. Kim, J.I.; Takahashi, M.; Ogura, A.; Kohno, T.; Kudo, Y.; Sato, K. Hydroxyl group of tyr13 is essential for the activity of ω-conotoxin gvia, a peptide toxin for N-type calcium channel. J. Biol. Chem. 1994, 269, 23876-23878.
87. Kim, J.I.; Takahashi, M.; Ohtake, A.; Wakamiya, A.; Sato, K., Tyr13 is essential for the activity of ω-conotoxin mviia and gvia, specific N-type calcium channel blockers. Biochem. Biophys. Res. Commun. 1995, 206, 449-454.
88. Olivera, B.M.; Gray, W.R.; Zeikus, R.; McIntosh, J.M.; Varga, J.; Rivier, J.; Santos, V.D.; Cruz, L.J. Peptide neurotoxins from fish-hunting cone snails. Science 1985, 230, 1338-1343.
89. Bingham, J.-P.; Baker, M.R.; Chun, J.B. Analysis of a cone snail's killer cocktail - the milked venom of conus geographus. Toxicon 2012, 60, 1166-1170.
90. Nielsen, K.J.; Schroeder, T.; Lewis, R. Structure-activity relationships of ω-conotoxins at N-type voltage-sensitive calcium channels. J. Mol. Recognit. 2000, 13, 55-70.
91. Wang, Y.X.; Bezprozvannaya, S.; Bowersox, S.S.; Nadasdi, L.; Miljanich, G.; Mezo, G.; Silva, D.; Tarczy-Hornoch, K.; Luther, R.R. Peripheral versus central potencies of N-type voltage-sensitive calcium channel blockers. Naunyn. Schmiedebergs. Arch. Pharmacol. 1998, 357, 159-168.
92. Chung, D.; Gaur, S.; Bell, J.R.; Ramachandran, J.; Nadasdi, L. Determination of disulfide bridge pattern in ω-conopeptides. Int. J. Pept. Protein. Res. 1995, 46, 320-325.
93. Lew, M.J.; Flinn, J.P.; Pallaghy, P.K.; Murphy, R.; Whorlow, S.L.; Wright, C.E.; Norton, R.S.; Angus, J.A. Structure-function relationships of ω-conotoxin gvia. Synthesis, structure, calcium channel binding, and functional assay of alanine-substituted analogues. J. Biol. Chem. 1997, 272, 12014-12023.
94. Flinn, J.P.; Pallaghy, P.K.; Lew, M.J.; Murphy, R.; Angus, J.A.; Norton, R.S. Roles of key functional groups in ω-conotoxin gvia synthesis, structure and functional assay of selected peptide analogues. Eur. J. Biochem. 1999, 262, 447-455.
95. Motin, L.; Yasuda, T.; Schroeder, C.I.; Lewis, R.J.; Adams, D.J. Ω-conotoxin inhibition of excitatory synaptic transmission evoked by dorsal root stimulation in rat superficial dorsal horn-conotoxin cvib differentially inhibits native and recombinant n- and p/q-type calciumchannels. Eur. J. Neurosci. 2007, 25, 435-444.
96. Motin, L.; Adams, D.J. Ω-conotoxin inhibition of excitatory synaptic transmission evoked by dorsal root stimulation in rat superficial dorsal horn. Neuropharmacology 2008, 55, 860-864.
97. Schroeder, K.; Neagle, B.; Trezise, D.J.; Worley, J. Ionworks ht: A new high-throughput electrophysiology measurement platform. J. Biomol. Screen 2003, 8, 50-64.
98. Swensen, A.M.; Niforatos, W.; Vortherms, T.A.; Perner, R.J.; Li, T.; Schrimpf, M.R.; Scott, V.E.; Lee, L.; Jarvis, M.F.; McGaraughty, S. An automated electrophysiological assay for differentiating Cav2. 2 inhibitors based on state dependence and kinetics. Assay Drug Develop. Technol. 2012, 10, 542-550.
99. Bauer, C.S.; Rahman, W.; Tran-van-Minh, A.; Lujan, R.; Dickenson, A.H.; Dolphin, A.C. The anti-allodynic α2δ ligand pregabalin inhibits the trafficking of the calcium channel α1b subunit to presynaptic terminals in vivo. Biochem. Soc. Trans. 2010, 38, 525-528.
100. Perret, D.; Luo, Z.D. Targeting voltage-gated calcium channels for neuropathic pain management. Neurotherapeutics 2009, 6, 679-692.
101. 2+ channels to nociceptive transmission in rat spinal lamina i neurons. Eur. J. Neurosci. 2004, 19, 103-111.
102. Rycroft, B.K.; Vikman, K.S.; Christie, M.J. Inflammation reduces the contribution of N-type calcium channels to primary afferent synaptic transmission onto nk1 receptor-positive lamina i neurons in the rat dorsal horn. J. Physiol. 2007, 580, 883-894.
103. Hockerman, G.H.; Johnson, B.D.; Abbott, M.R.; Scheuer, T.; Catterall, W.A. Molecular determinants of high affinity phenylalkylamine block of l-type calcium channels in transmembrane segment iiis6 and the pore region of the α1 subunit. J. Biol. Chem. 1997, 272, 18759-18765.
104. McGuire, D.; Bowersox, S.; Fellmann, J.D.; Luther, R.R. Sympatholysis after neuron-specific, N-type, voltage-sensitive calcium channel blockade: First demonstration of n-channel function in humans. J. Cardiovasc. Pharmacol. 1997, 30, 400-403.
105. Escoubas, P.; Sollod, B.; King, G.F. Venom landscapes: Mining the complexity of spider venoms via a combined cdna and mass spectrometric approach. Toxicon 2006, 47, 650-663.
106. Estrada, G.; Villegas, E.; Corzo, G. Spider venoms: A rich source of acylpolyamines and peptides as new leads for cns drugs. Nat. Product Rep. 2007, 24, 145-161.
107. Norton, R.S.; McDonough, S.I. Peptides targeting voltage-gated calcium channels. Curr. Pharm. Des. 2008, 14, 2480-2491.
108. Mintz, I.M.; Venema, V.J.; Swiderek, K.M.; Lee, T.D.; Bean, B.P.; Adams, M.E. P-type calcium channels blocked by the spider toxin omega-aga-iva. Nature 1992, 355, 827-829.
109. Newcomb, R.; Szoke, B.; Palma, A.; Wang, G.; Chen, X.; Hopkins, W.; Cong, R.; Miller, J.; Urge, L.; Tarczy-Hornoch, K.; et al. Selective peptide antagonist of the class e calcium channel from the venom of the tarantula hysterocrates gigas. Biochemistry 1998, 37, 15353-15362.
110. Wang, M.; Guan, X.; Liang, S. The cross channel activities of spider neurotoxin huwentoxin-i on rat dorsal root ganglion neurons. Biochem. Biophys. Res. Commun. 2007, 357, 579-583.
111. Liang, S.P.; Zhang, D.Y.; Pan, X.; Chen, Q.; Zhou, P.A. Properties and amino acid sequence of huwentoxin-i, a neurotoxin purified from the venom of the chinese bird spider selenocosmia huwena. Toxicon 1993, 31, 969-978.
112. Jiang, L.; Peng, L.; Chen, J.; Zhang, Y.; Xiong, X.; Liang, S. Molecular diversification based on analysis of expressed sequence tags from the venom glands of the chinese bird spider ornithoctonus huwena. Toxicon 2008, 51, 1479-1489.
113. Liu, Z.; Dai, J.; Dai, L.; Deng, M.; Hu, Z.; Hu, W.; Liang, S., Function and solution structure of huwentoxin-x, a specific blocker of N-type calcium channels, from the chinese bird spider ornithoctonus huwena. J. Biol. Chem. 2006, 281, 8628-8635.
114. Bindokas, V.P.; Adams, M.E. Ω-aga-i: A presynaptic calcium channel antagonist from venom of the funnel web spider, agelenopsis aperta. J. Neurobiol. 1989, 20, 171-188.
115. Adams, M.E.; Bindokas, V.P.; Hasegawa, L.; Venema, V.J. Ω-agatoxins: Novel calcium channel antagonists of two subtypes from funnel web spider (agelenopsis aperta) venom. J. Biol. Chem. 1990, 265, 861-867.
116. Ertel, E.A.; Warren, V.A.; Adams, M.E.; Griffin, P.R.; Cohen, C.J.; Smith, M.M. Type iii. Ω-agatoxins: A family of probes for similar binding sites on l- and N-type calcium channels. Biochemistry 1994, 33, 5098-5108.
117. Yan, L.; Adams, M.E. The spider toxin ω-aga iiia defines a high affinity site on neuronal high voltage-activated calcium channels. J. Biol. Chem. 2000, 275, 21309-21316.
118. Leao, R.M.; Cruz, J.S.; Diniz, C.R.; Cordeiro, M.N.; Beirao, P.S. Inhibition of neuronal high-voltage activated calcium channels by the omega-phoneutria nigriventer tx3-3 peptide toxin. Neuropharmacology 2000, 39, 1756-1767.
119. Cordeiro Mdo, N.; de Figueiredo, S.G.; Valentim Ado, C.; Diniz, C.R.; von Eickstedt, V.R.; Gilroy, J.; Richardson, M. Purification and amino acid sequences of six tx3 type neurotoxins from the venom of the brazilian 'armed' spider phoneutria nigriventer (keys). Toxicon 1993, 31, 35-42.
120. Vieira, L.B.; Kushmerick, C.; Hildebrand, M.E.; Garcia, E.; Stea, A.; Cordeiro, M.N.; Richardson, M.; Gomez, M.V.; Snutch, T.P. Inhibition of high voltage-activated calcium channels by spider toxin pntx3-6. J. Pharmacol. Exp. Ther. 2005, 314, 1370-1377.
121. 2+ currents activation induced by a new toxin from phoneutria reidyi (aranae, ctenidae) venom. Cell. Mol. Neurobiol. 2007, 27, 129-146.
122. Richardson, M.; Pimenta, A.M.; Bemquerer, M.P.; Santoro, M.M.; Beirao, P.S.; Lima, M.E.; Figueiredo, S.G.; Bloch, C., Jr.; Vasconcelos, E.A.; Campos, F.A.; et al. Comparison of the partial proteomes of the venoms of brazilian spiders of the genus phoneutria. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 2006, 142, 173-187.
123. Newcomb, R.; Palma, A.; Fox, J.; Gaur, S.; Lau, K.; Chung, D.; Cong, R.; Bell, J.R.; Horne, B.; Nadasdi, L.; et al. Snx-325, a novel calcium antagonist from the spider segestria florentina. Biochemistry 1995, 34, 8341-8347.
124. v2.2) mediated Calcium mobilization using flipr. Biochem. Pharmacol. 2006, 72, 770-782.
125. Adams, M.E.; Mintz, I.M.; Reily, M.D.; Thanabal, V.; Bean, B.P., Structure and properties of ω-agatoxin ivb, a new antagonist of p-type calcium channels. Mol. Pharmacol. 1993, 44, 681-688.
126. Cardoso, F.C.; Pacifico, L.G.; Carvalho, D.C.; Victoria, J.M.; Neves, A.L.; Chavez-Olortegui, C.; Gomez, M.V.; Kalapothakis, E. Molecular cloning and characterization of phoneutria nigriventer toxins active on calcium channels. Toxicon 2003, 41, 755-763.
127. 2+-dependent glutamate release in synaptosomes. Neurochem. Int. 2003, 42, 277-282.
128. Souza, A.H.; Ferreira, J.; Cordeiro Mdo, N.; Vieira, L.B.; De Castro, C.J.; Trevisan, G.; Reis, H.; Souza, I.A.; Richardson, M.; Prado, M.A.; et al., Analgesic effect in rodents of native and recombinant ph α1β toxin, a high-voltage-activated calcium channel blocker isolated from armed spider venom. Pain 2008, 140, 115-126.
129. de Souza, A.H.; Lima, M.C.; Drewes, C.C.; da Silva, J.F.; Torres, K.C.; Pereira, E.M.; de Castro Junior, C.J.; Vieira, L.B.; Cordeiro, M.N.; Richardson, M.; et al. Antiallodynic effect and side effects of pα1β, a neurotoxin from the spider phoneutria nigriventer: Comparison with ω-conotoxin mviia and morphine. Toxicon 2011, 58, 626-633.
130. Dalmolin, G.D.; Silva, C.R.; Rigo, F.K.; Gomes, G.M.; Cordeiro Mdo, N.; Richardson, M.; Silva, M.A.; Prado, M.A.; Gomez, M.V.; Ferreira, J. Antinociceptive effect of brazilian armed spider venom toxin tx3-3 in animal models of neuropathic pain. Pain 2011, 152, 2224-2232.
131. 2+ channel mutant mouse, rolling mouse nagoya. Neuroscience 2009, 160, 165-173.
132. Todorovic, S.M.; Jevtovic-Todorovic, V. T-type voltage-gated calcium channels as targets for the development of novel pain therapies. Br. J. Pharmacol. 2011, 163, 484-495.
133. Olivera, B.M.; Miljanich, G.P.; Ramachandran, J.; Adams, M.E., Calcium channel diversity and neurotransmitter release: The omega-conotoxins and omega-agatoxins. Annu. Rev. Biochem. 1994, 63, 823-867.
134. Stotz, S.C.; Spaetgens, R.L.; Zamponi, G.W. Block of voltage-dependent calcium channel by the green mamba toxin calcicludine. J. Membr. Biol. 2000, 174, 157-165.
135. 2+ channels. J. Neurosci. 2002, 22, 2023-2034.
136. 2+ channel activity. EMBO J. 2002, 21, 6733-6743.
137. Lee, C.W.; Eu, Y.J.; Min, H.J.; Cho, E.M.; Lee, J.H.; Kim, H.H.; Nah, S.Y.; Swartz, K.J.; Kim, J.I., Expression and characterization of recombinant kurtoxin, an inhibitor of t-type voltage-gated calcium channels. Biochem. Biophys. Res. Commun. 2011, 416, 277-282.
138. de Weille, J.R.; Schweitz, H.; Maes, P.; Tartar, A.; Lazdunski, M. Calciseptine, a peptide isolated from black mamba venom, is a specific blocker of the l-type calcium channel. Proc. Natl. Acad. Sci. USA 1991, 88, 2437-2440.
139. 2+ channels with a high affinity for l-type channels in cerebellar granule neurons. Proc. Natl. Acad. Sci. USA 1994, 91, 878-882.
140. Yang, S.; Liu, Z.; Xiao, Y.; Li, Y.; Rong, M.; Liang, S.; Zhang, Z.; Yu, H.; King, G.F.; Lai, R. Chemical punch packed in venoms makes centipedes excellent predators. Mol. Cell. Proteom. 2012, 11, 640-650.
141. Corzo, G.; Adachi-Akahane, S.; Nagao, T.; Kusui, Y.; Nakajima, T. Novel peptides from assassin bugs (hemiptera: Reduviidae): Isolation, chemical and biological characterization., FEBS Lett. 2001, 499, 256-261.
142. Bernard, C.; Corzo, G.; Mosbah, A.; Nakajima, T.; Darbon, H. Solution structure of ptu1, a toxin from the assassin bug peirates turpis that blocks the voltage-sensitive calcium channel N-type. Biochemistry 2001, 40, 12795-12800.
143. Vetter, I.; Davis, J.L.; Rash, L.D.; Anangi, R.; Mobli, M.; Alewood, P.F.; Lewis, R.J.; King, G.F. Venomics: A new paradigm for natural products-based drug discovery. Amino Acids 2011, 40, 15-28.
144. Finley, M.F.; Lubin, M.L.; Neeper, M.P.; Beck, E.; Liu, Y.; Flores, C.M.; Qin, N. An integrated multiassay approach to the discovery of small-molecule N-type voltage-gated calcium channel antagonists. Assay Drug Dev. Technol. 2010, 8, 685-694.
145. Dai, G.; Haedo, R.J.; Warren, V.A.; Ratliff, K.S.; Bugianesi, R.M.; Rush, A.; Williams, M.E.; Herrington, J.; Smith, M.M.; McManus, O.B.; et al. A high-throughput assay for evaluating state dependence and subtype selectivity of Cav2 calcium channel inhibitors. Assay Drug Dev. Technol. 2008, 6, 195-212.
146. Dunlop, J.; Bowlby, M.; Peri, R.; Tawa, G.; LaRocque, J.; Soloveva, V.; Morin, J. Ion channel screening. Comb. Chem. High Throughput Screen. 2008, 11, 514-522.
147. Lubin, M.L.; Reitz, T.L.; Todd, M.J.; Flores, C.M.; Qin, N.; Xin, H. A nonadherent cell-based hts assay for N-type calcium channel using calcium 3 dye. Assay Drug Dev. Technol. 2006, 4, 689-694.
148. v2.2 voltage-gated calcium channels for neuropathic pain. Biochem. Pharmacol. 2005, 70, 489-499.
149. v2.2 Channels. In Proceedings of 17th World Congress the International Society on Toxinology & Venom Week 2012, Honolulu, Hawaii, USA, 8-13 July 2012; Volume 60, p. 111.