Venomous Peptides as Cardiac Ion Channel’s Modulators

Sree   Vandana   Yerramsetty; Hitesh      Chopra; Viajaya   Nirmala   Pangi; Veera   Bramhachari   Pallaval; Anitha      Jaganathan; Yugal   Kishore   Mohanta; Mohammad   Amjad   Kamal; Sunil      Junapudi
Abstract

Venoms from the deadliest animals, including spiders, scorpians, bees, and centipedes, are composed of a complex mixture of various peptides developed to catch prey and defend other animals. Venoms are composed of several bioactive molecules such as proteins and peptides that modify physiological conditions in other organisms. These bioactive peptides penetrate tissues and blood vessels to encounter numerous receptors and modulate ion channel their activities. Venoms are used to treat various medical issues, including cardiovascular diseases. Venom peptides regulate several ion channel behaviors, such as voltage-gated sodium (Nav), calcium (Cav) and potassium (Kv) channels, and are set as a therapeutic approach. In this perspective, we emphasize the effect of isolated lethal venomous peptides on cardiac ionic channels and their mechanisms of action for the cure. We also summarize the highlights and molecular details of their toxin-receptor interactions and prospects to develop peptide therapeutics for respective cardiac electrophysiological diseases.
Keywords: Venoms, peptides, cardiac diseases, ion channels, currents, voltage gated channels.
Graphical Abstract

[1]
Walker AA, Robinson SD, Hamilton BF, Undheim EAB, King GF. Deadly proteomes: A practical guide to proteotranscriptomics of animal venoms. Proteomics  2020; 20(17-18): e1900324.
 [http://dx.doi.org/10.1002/pmic.201900324] [PMID:  32820606]

[2]
Lewis RJ, Garcia ML. Therapeutic potential of venom peptides. Nat Rev Drug Discov  2003; 2(10): 790-802. Available from: www.nature.com/reviews/drugdisc
 [http://dx.doi.org/10.1038/nrd1197] [PMID:  14526382]

[3]
Zhao F, Lan X, Li T, Xiang Y, Zhao F, Zhang Y. Proteotranscriptomic analysis and discovery of the profile and diversity of toxin-like proteins in centipede. Mol Cell Proteomics Elsevier Inc.   2018; 17: pp. 709-20.
 [http://dx.doi.org/10.1074/mcp.RA117.000431]

[4]
Chu Y, Qiu P, Yu R. Toxins centipede venom peptides acting on ion channels. Toxins (Basel)  2020; 12(4): 1-18. Available from: www.mdpi.com/journal/toxins
 [http://dx.doi.org/10.3390/toxins12040230]

[5]
King GF. Venoms as a platform for human drugs: translating toxins into therapeutics. Expert Opin Biol Ther  2011; 11(11): 1469-84.
 [http://dx.doi.org/10.1517/14712598.2011.621940] [PMID:  21939428]

[6]
Olivera BM, Essay EEEE. Just Lecture, 1996. Conus venom peptides, receptor and ion channel targets, and drug design: 50 million years of neuropharmacology. Mol Biol Cell  1997; 8(11): 2101-9.
 [http://dx.doi.org/10.1091/mbc.8.11.2101] [PMID:  9362055]

[7]
Dutertre SÃ, Lewis RJ. Use of Venom Peptides to Probe ion channels structure and function. J Biol Chem  2010; 285: 13315-20.
 [http://dx.doi.org/10.1074/jbc.R109.076596]

[8]
Baron A, Diochot S, Salinas M, Deval E, Noël J, Lingueglia E. Venom toxins in the exploration of molecular, physiological and pathophysiological functions of acid-sensing ion channels. Toxicon Pergamon  2013; 75: 187-204.
 [http://dx.doi.org/10.1016/j.toxicon.2013.04.008] [PMID:  23624383]

[9]
Rong M, Yang S, Wen B, Mo G, Kang D, Liu J. Peptidomics combined with cDNA library unravel the diversity of centipede venom. J Proteomics  2015; 114: 28-37.

[10]
González-Morales L, Pedraza-Escalona M, Diego-Garcia E, Restano-Cassulini R, Batista CVF, Gutiérrez M del C. Proteomic characterization of the venom and transcriptomic analysis of the venomous gland from the Mexican centipede Scolopendra viridis. J Proteomics  2014; 111: 224-37.

[11]
Terlau H, Olivera BM. Conus venoms: A rich source of novel ion channel-targeted peptides. Physiol Rev  2004; 84(1): 41-68.
 [http://dx.doi.org/10.1152/physrev.00020.2003] [PMID:  14715910]

[12]
Sonoda Y, Hada N, Kaneda T, et al. A synthetic glycosphingolipid-induced antiproliferative effect in melanoma cells is associated with suppression of FAK, Akt, and Erk activation. Biol Pharm Bull  2008; 31(6): 1279-83.
 [http://dx.doi.org/10.1248/bpb.31.1279] [PMID:  18520069]

[13]
Cheng J, Wen J, Wang N, Wang C, Xu Q, Yang Y. Ion Channels and vascular diseases. Arterioscler Thromb Vasc Biol  2019; 39(5): e146-56.
 [http://dx.doi.org/10.1161/ATVBAHA.119.312004] [PMID:  31017824]

[14]
Catterall WA. Structure and function of voltage-gated ion channels. Annu Rev Biochem  1995; 64: 493-531.
 [http://dx.doi.org/10.1146/annurev.bi.64.070195.002425] [PMID:  7574491]

[15]
Yu S, Li G, Huang CL-H, Lei M, Wu L. Late sodium current associated cardiac electrophysiological and mechanical dysfunction. Pflugers Arch  2018; 470(3): 461-9.
 [http://dx.doi.org/10.1007/s00424-017-2079-7] [PMID:  29127493]

[16]
Ufret-Vincenty CA, Baro DJ, Lederer WJ, Rockman HA, Quiñones LE, Santana LF. Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure. J Biol Chem  2001; 276(30): 28197-203.
 [http://dx.doi.org/10.1074/jbc.M102548200] [PMID:  11369778]

[17]
Roth GA, Johnson CO, Abate KH, et al. Global Burden of Cardiovascular Diseases Collaboration. The burden of cardiovascular diseases among US States, 1990-2016. JAMA Cardiol  2018; 3(5): 375-89.
 [http://dx.doi.org/10.1001/jamacardio.2018.0385] [PMID:  29641820]

[18]
Ferraz CR, Arrahman A, Xie C, et al. Multifunctional toxins in snake venoms and therapeutic implications: From pain to hemorrhage and necrosis. Front Ecol Evol  2019; 7: 218. Available from: https://www.frontiersin.org/article/10.3389/fevo.2019.00218 [Internet]
 [http://dx.doi.org/10.3389/fevo.2019.00218]

[19]
Pal SK, Gomes A, Dasgupta SC, Gomes A. Snake venom as therapeutic agents: From toxin to drug development. Indian J Exp Biol  2002; 40(12): 1353-8.
 [PMID:  12974396]

[20]
Konshina AG, Krylov NA, Efremov RG. Cardiotoxins: Functional role of local conformational changes. J Chem Inf Model  2017; 57: 2799-810.
 [http://dx.doi.org/10.1021/acs.jcim.7b00395]

[21]
Kini RM, Koh CY. Snake venom three-finger toxins and their potential in drug development targeting cardiovascular diseases. Biochem Pharmacol  2020; 181: 114105.
 [http://dx.doi.org/10.1016/j.bcp.2020.114105] [PMID:  32579959]

[22]
Song W, Shou W. Cardiac sodium channel Nav1.5 mutations and cardiac arrhythmia. Pediatr Cardiol  2012; 33(6): 943-9.
 [http://dx.doi.org/10.1007/s00246-012-0303-y] [PMID:  22460359]

[23]
Han D, Tan H, Sun C, Li G. Dysfunctional Nav1.5 channels due to SCN5A mutations. Exp Biol Med (Maywood)  2018; 243(10): 852-63.
 [http://dx.doi.org/10.1177/1535370218777972] [PMID:  29806494]

[24]
Wu Z, Yang Y, Xie L, et al. Toxicity and distribution of tetrodotoxin-producing bacteria in puffer fish Fugu rubripes collected from the Bohai sea of China. Toxicon  2005; 46(4): 471-6.
 [http://dx.doi.org/10.1016/j.toxicon.2005.06.002] [PMID:  16051296]

[25]
Wu Y, Ma H, Zhang F, Zhang C, Zou X, Cao Z. Selective voltage-gated sodium channel peptide toxins from animal venom: Pharmacological probes and analgesic drug development. ACS Chem Neurosci  2018; 9: 187-97.
 [http://dx.doi.org/10.1021/acschemneuro.7b00406]

[26]
Liavas A, Lignani G, Schorge S. Conservation of alternative splicing in sodium channels reveals evolutionary focus on release from inactivation and structural insights into gating. J Physiol  2017; 595(16): 5671-85.
 [http://dx.doi.org/10.1113/JP274693] [PMID:  28621020]

[27]
Gonçalves TC, Boukaiba R, Molgó J, et al. Direct evidence for high affinity blockade of NaV1.6 channel subtype by huwentoxin-IV spider peptide, using multiscale functional approaches. Neuropharmacology  2018; 133: 404-14.
 [http://dx.doi.org/10.1016/j.neuropharm.2018.02.016] [PMID:  29474819]

[28]
Priest BT, Blumenthal KM, Smith JJ, Warren VA, Smith MM. ProTx-I and ProTx-II: Gating modifiers of voltage-gated sodium channels. Toxicon  2007; 49(2): 194-201.
 [http://dx.doi.org/10.1016/j.toxicon.2006.09.014] [PMID:  17087985]

[29]
Middleton RE, Warren VA, Kraus RL, Hwang JC, Liu CJ, Dai G. Two tarantula peptides inhibit activation of multiple sodium channels. Biochemistry  2002; 41: 14734-47.
 [http://dx.doi.org/10.1021/bi026546a]

[30]
Li X. Animal toxins influence voltage-gated sodium channel. Physiol Behav 2016.

[31]
Belcher S, Zerillo C, Levenson R, Ritchie J, Howe J, Pande VS, et al. Cloning of a sodium channel alpha subunit from rabbit Schwann cells. PNAS  2012; 92: 11034-8. Available from: https://www.pnas.org/content/109/44/18102

[32]
Jiang D, Tonggu L, Gamal El-Din TM, et al. Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin. Nat Commun  2021; 12(1): 128.
 [http://dx.doi.org/10.1038/s41467-020-20078-3] [PMID:  33397917]

[33]
Lopez L, Montnach J, Nicolas S, Jaquillard L, Beroud R, De Waard M. High-throughput screening of animal venoms for identification of compounds active on the cardiac Nav1.5 channel. Arch Cardiovasc Dis Suppl. Elsevier Masson  2020; 12: 258-9.

[34]
Medler S. Anesthetic MS-222 eliminates nerve and muscle activity in frogs used for physiology teaching laboratories. Adv Physiol Educ  2019; 43(1): 69-75.
 [http://dx.doi.org/10.1152/advan.00114.2018] [PMID:  30694709]

[35]
Huang W-C, Hsieh Y-S, Chen I-H, Wang C-H, Chang H-W, Yang C-C. Combined use of MS-222 (Tricaine) and isoflurane extends anesthesia time and minimizes cardiac rhythm side effects in adult zebrafish. Zebrafish  2010; 7: 297-304.
 [http://dx.doi.org/10.1089/zeb.2010.0653]

[36]
Sansom MSP, Shrivastava IH, Bright JN, Tate J, Capener CE, Biggin PC. Potassium channels: Structures, models, simulations. Biochim Biophys Acta Biomembr  2002; 1565: 294-307.
 [http://dx.doi.org/10.1016/S0005-2736(02)00576-X]

[37]
Yellen G. The voltage-gated potassium channels and their relatives. Nature  2002; 419(6902): 35-42.
 [http://dx.doi.org/10.1038/nature00978] [PMID:  12214225]

[38]
Kuang Q, Purhonen P, Hebert H. Structure of potassium channels. Cell Mol Life Sci  2015; 72(19): 3677-93.
 [http://dx.doi.org/10.1007/s00018-015-1948-5] [PMID:  26070303]

[39]
Yarov-Yarovoy V, Baker D, Catterall WA. Voltage sensor conformations in the open and closed states in ROSETTA structural models of K channels. Proceedings of the National Academy of Sciences  2006; 103(19): 7292-. Available from: http://www.pnas.orgcgidoi10.1073pnas.0602350103

[40]
Guéguinou M, ChantÔme A, Fromont G, et al. KCa and Ca2+ channels: The complex thought. Biochim Biophys Acta Mol Cell Res  2014; 1843: 2322-33.

[41]
Tamargo J, Caballero R, Gómez R, Valenzuela C, Delpón E. Pharmacology of cardiac potassium channels. Cardiovasc Res  2004; 62(1): 9-33.
 [http://dx.doi.org/10.1016/j.cardiores.2003.12.026] [PMID:  15023549]

[42]
Schmitt N, Grunnet M, Olesen S-P. Cardiac potassium channel subtypes: New roles in repolarization and arrhythmia. Physiol Rev 2014.
 [http://dx.doi.org/10.1152/physrev.00022.2013]

[43]
Grant AO. Basic science for the clinical electrophysiologist cardiac ion channels the cardiac action potential general properties of ion channels. Circ Arrhythm Electrophysiol  2009; 2: 185-94. Available from: http://ahajournals.org

[44]
Klint JK, Senff S, Rupasinghe DB, et al. Spider-venom peptides that target voltage-gated sodium channels: Pharmacological tools and potential therapeutic leads. Toxicon Pergamon  2012; 60(4): 478-91.
 [http://dx.doi.org/10.1016/j.toxicon.2012.04.337] [PMID:  22543187]

[45]
Csoti A, Alvarado D, Cardoso-Arenas S, et al. Novel spider peptide that affects the voltage gated potassium channel kv1.5. Biophys J  2021; 120(3): 246a-7a.
 [http://dx.doi.org/10.1016/j.bpj.2020.11.1610]

[46]
Vandenberg JI, Perry MD, Perrin MJ, Mann SA, Ke Y, Hill AP. hERG K+ channels: Structure, function, and clinical significance. Physiol Rev  2012; 92: 1393-478.
 [http://dx.doi.org/10.1152/physrev.00036.2011]

[47]
Wanke E, Restano-Cassulini R. Toxins interacting with ether-à-go-go-related gene voltage-dependent potassium channels. Toxicon  2007; 49(2): 239-48.
 [http://dx.doi.org/10.1016/j.toxicon.2006.09.025] [PMID:  17097705]

[48]
Gunay BC, Yurtsever M, Durdagi S. Elucidation of interaction mechanism of hERG1 potassium channel with scorpion toxins BeKm-1 and BmTx3b. J Mol Graph Model  2020; 96: 107504.

[49]
Angelo K, Korolkova YV, Grunnet M, et al. A radiolabeled peptide ligand of the hERG channel, [125I]-BeKm-1. Pflugers Arch  2003; 447(1): 55-63.
 [http://dx.doi.org/10.1007/s00424-003-1125-9] [PMID:  12905030]

[50]
Evans MH. Mechanism of saxitoxin and tetrodotoxin poisoning. Br Med Bull  1969; 25(3): 263-7.
 [http://dx.doi.org/10.1093/oxfordjournals.bmb.a070715] [PMID:  5812102]

[51]
Wang J, Salata JJ, Bennett PB. Saxitoxin is a gating modifier of HERG K+ channels. J Gen Physiol  2003; 121(6): 583-98.
 [http://dx.doi.org/10.1085/jgp.200308812] [PMID:  12771193]

[52]
Wang Y, Luo Z, Lei S, Li S, Li X, Yuan C. Effects and mechanism of gating modifier spider toxins on the hERG channel. Toxicon Pergamon  2021; 189: 56-64.
 [http://dx.doi.org/10.1016/j.toxicon.2020.11.008] [PMID:  33212100]

[53]
Kanjhan R, Coulson EJ, Adams DJ, Bellingham MC. Tertiapin-Q blocks recombinant and native large conductance K+ channels in a use-dependent manner. J Pharmacol Exp Ther  2005; 314(3): 1353-61.
 [http://dx.doi.org/10.1124/jpet.105.085928] [PMID:  15947038]

[54]
Isomoto S, Kondo C, Kurachi Y. Inwardly rectifying potassium channels: Their molecular heterogeneity and function. Jpn J Physiol  1997; 47(1): 11-39.
 [http://dx.doi.org/10.2170/jjphysiol.47.11] [PMID:  9159640]

[55]
Bidaud I, Chong ACY, Carcouet A, et al. Inhibition of G protein-gated K+ channels by tertiapin-Q rescues sinus node dysfunction and atrioventricular conduction in mouse models of primary bradycardia. Sci Rep  2020; 10(1): 9835.
 [http://dx.doi.org/10.1038/s41598-020-66673-8] [PMID:  32555258]

[56]
Yu H, Lin Z, Mattmann ME, Zou B, Terrenoire C, Zhang H. Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels. Proc Natl Acad Sci  2013; 110: 8732-7. Available from: https://www.pnas.org/content/110/21/8732
 [http://dx.doi.org/10.1073/pnas.1300684110]

[57]
Liu Z-C, Zhang R, Zhao F, Chen Z-M, Liu H-W, Wang Y-J. Venomic and transcriptomic analysis of centipede scolopendra subspinipes dehaani. J Proteome Res  2012; 11: 6197-212.
 [http://dx.doi.org/10.1021/pr300881d]

[58]
Luo L, Li B, Wang S, Wu F, Wang X, Liang P. Centipedes subdue giant prey by blocking KCNQ channels. Proc Natl Acad Sci USA  2018; 115: 1646-51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29358396
 [http://dx.doi.org/10.1073/pnas.1714760115]

[59]
Dash TS, Shafee T, Harvey PJ, et al. A centipede toxin family defines an ancient class of csαβ defensins. Cell Press  2019; 27(2): 315-326.e7.
 [http://dx.doi.org/10.1016/j.str.2018.10.022] [PMID:  30554841]

[60]
Chen M, Li J, Zhang F, Liu Z. Isolation and characterization of SsmTx-I, a Specific Kv2.1 blocker from the venom of the centipede Scolopendra Subspinipes Mutilans L. Koch. Ltd  2014; 20(3): 159-64.
 [http://dx.doi.org/10.1002/psc.2588] [PMID:  24464516]

[61]
Öztekin Long M. Bone  2008; 23: 1-7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624763/pdf/nihms412728.pdf

[62]
Catterall WA. Voltage-gated calcium channels. Cold Spring Harb Perspect Biol  2011; 3(8): a003947.
 [http://dx.doi.org/10.1101/cshperspect.a003947] [PMID:  21746798]

[63]
Laver DR. Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites. Biophys J  2007; 92(10): 3541-55.
 [http://dx.doi.org/10.1529/biophysj.106.099028] [PMID:  17351009]

[64]
Lee S. Pharmacological inhibition of voltage-gated Ca2+ channels for chronic pain relief. Curr Neuropharmacol  2013; 11(6): 606-20.
 [http://dx.doi.org/10.2174/1570159X11311060005] [PMID:  24396337]

[65]
Diochot S, Richard S, Baldy-Moulinier M, Nargeot J, Valmier J. Dihydropyridines, phenylalkylamines and benzothiazepines block N-, P/Q- and R-type calcium currents. Pflugers Arch  1995; 431(1): 10-9.
 [http://dx.doi.org/10.1007/BF00374372] [PMID:  8584405]

[66]
Hwang I-W, Shin MK, Lee Y-J, et al. N-type Cav channel inhibition by spider venom peptide of Argiope bruennichi. Mol Cell Toxicol  2021; 17(1): 59-67.
 [http://dx.doi.org/10.1007/s13273-020-00109-2]

[67]
Cardoso FC, Castro J, Grundy L, et al. A spider-venom peptide with multitarget activity on sodium and calcium channels alleviates chronic visceral pain in a model of irritable bowel syndrome. Pain  2021; 162(2): 569-81. Available from: https://journals.lww.com/pain/Fulltext/2021/02000/A_spider_venom_peptide_with_multitarget_activity.22.aspx
 [http://dx.doi.org/10.1097/j.pain.0000000000002041] [PMID:  32826759]

[68]
Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J. International union of pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev  2005; 57(4): 411-25. Available from: http://pharmrev.aspetjournals.org
 [http://dx.doi.org/10.1124/pr.57.4.5] [PMID:  16382099]

[69]
Quintero-Hernández V, Jiménez-Vargas JM, Gurrola GB, Valdivia HH, Possani LD. Scorpion venom components that affect ion-channels function. Toxicon Pergamon  2013; 76: 328-42.
 [http://dx.doi.org/10.1016/j.toxicon.2013.07.012] [PMID:  23891887]

[70]
Vieira LB, Kushmerick C, Hildebrand ME, Garcia E, Stea A, Cordeiro MN, et al. Inhibition of high voltage-activated calcium channels by spider toxin PnTx3-6. J Pharmacol Exp Ther  2005; 314: 1370-7. Available from: http://jpet.aspetjournals.org/content/314/3/1370 abstract

[71]
Leão RM, Cruz JS, Diniz CR, Cordeiro MN, Beirão PSL. Inhibition of neuronal high-voltage activated calcium channels by the ω-phoneutria nigriventer Tx3-3 peptide toxin. Neuropharmacology  2000; 39(10): 1756-67.
 [http://dx.doi.org/10.1016/S0028-3908(99)00267-1] [PMID:  10884557]

[72]
Bourinet E, Stotz SC, Spaetgens RL, et al. Interaction of SNX482 with domains III and IV inhibits activation gating of α(1E) (Ca(V)2.3) calcium channels. Biophys J  2001; 81(1): 79-88.
 [http://dx.doi.org/10.1016/S0006-3495(01)75681-0] [PMID:  11423396]

[73]
Tottene A, Volsen S, Pietrobon D. Subunits form the pore of three cerebellar R-type calcium channels with different pharmacological and permeation properties. J Neurosci  2000; 20: 171-8. Available from: http://www.jneurosci.org/content/20/1/171 abstract

[74]
Peng K, Chen XD, Liang SP. The effect of Huwentoxin-I on Ca(2+) channels in differentiated NG108-15 cells, a patch-clamp study. Toxicon  2001; 39(4): 491-8.
 [http://dx.doi.org/10.1016/S0041-0101(00)00150-1] [PMID:  11024489]

[75]
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: 579-83.
 [http://dx.doi.org/10.1016/j.bbrc.2007.02.168]

[76]
Cherki RS, Kolb E, Langut Y, Tsveyer L, Bajayo N, Meir A. Two tarantula venom peptides as potent and differential Na(V) channels blockers. Toxicon Pergamon  2014; 77: 58-67.
 [http://dx.doi.org/10.1016/j.toxicon.2013.10.029] [PMID:  24211312]

[77]
Cardoso FC. Multi-targeting sodium and calcium channels using venom peptides for the treatment of complex ion channels-related diseases. Biochem Pharmacol  2020; 181: 114107.
 [http://dx.doi.org/10.1016/j.bcp.2020.114107] [PMID:  32579958]

[78]
Souza AH, Ferreira J, Cordeiro M do N, et al. Analgesic effect in rodents of native and recombinant Phα1β toxin, a high-voltage-activated calcium channel blocker isolated from armed spider venom. Pain  2008; 140: 115-26.

[79]
Doupnik CA. Venom-derived peptides inhibiting Kir channels: Past, present, and future. Neuropharmacology  2017; 127: 161-72.
 [http://dx.doi.org/10.1016/j.neuropharm.2017.07.011] [PMID:  28716449]

[80]
Yi H, Cao Z, Yin S, Dai C, Wu Y, Li W. Interaction simulation of hERG K+ channel with its specific BeKm-1 Peptide:  Insights into the selectivity of molecular recognition. J Proteome Res  2007; 6: 611-20.
 [http://dx.doi.org/10.1021/pr060368g]

[81]
Suchyna TM, Johnson JH, Hamer K, et al. Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. J Gen Physiol  2000; 115(5): 583-98.
 [http://dx.doi.org/10.1085/jgp.115.5.583] [PMID:  10779316]

[82]
Filippovich I, Sorokina N, Masci PP, et al. A family of textilinin genes, two of which encode proteins with antihaemorrhagic properties. Br J Haematol  2002; 119(2): 376-84.
 [http://dx.doi.org/10.1046/j.1365-2141.2002.03878.x] [PMID:  12406072]

[83]
Bode F, Sachs F, Franz MR. Tarantula peptide inhibits atrial fibrillation. Nature  2001; 409(6816): 35-6.
 [http://dx.doi.org/10.1038/35051165] [PMID:  11343101]

[84]
Sharpe IA, Gehrmann J, Loughnan ML, et al. Two new classes of conopeptides inhibit the α1-adrenoceptor and noradrenaline transporter. Nat Neurosci  2001; 4(9): 902-7.
 [http://dx.doi.org/10.1038/nn0901-902] [PMID:  11528421]

[85]
Sharpe IA, Thomas L, Loughnan M, Motin L, Palant E, Croker DE. Allosteric α1-adrenoreceptor antagonism by the conopeptide ρ-TIA. J Biol Chem  2003; 278: 34451-7.
 [http://dx.doi.org/10.1074/jbc.M305410200]

[86]
Nicolas JP, Lin Y, Lambeau G, Ghomashchi F, Lazdunski M, Gelb MH. Localization of structural elements of bee venom phospholipase A2 involved in N-type receptor binding and neurotoxicity. J Biol Chem  1997; 272: 7173-81.
 [http://dx.doi.org/10.1074/jbc.272.11.7173]

[87]
Džavík V, Lavi S, Thorpe K, Yip PM, Plante S, Ing D, et al. Interventional cardiology The sPLA 2 inhibition to decrease enzyme release after percutaneous coronary intervention (SPIDERPCI) trial. Circ is  2010; 122: 2411-8. Available from: http://circ.ahajournals.org
Cite As
Venoms and Toxins

Venomous Peptides as Cardiac Ion Channel’s Modulators

Abstract

Graphical Abstract
