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Viperidae snake venoms block nicotinic acetylcholine receptors and voltage-gated Ca2+ channels in identified neurons of fresh-water snail Lymnaea stagnalis

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Snake venoms contain a vast array of toxic polypeptide components interacting with a variety of cell targets. Thus, Elapidae snake venoms contain α-neurotoxins with very high affinity for nicotinic acetylcholine receptors (nAChRs) and a few toxins able to suppress the activity of Ca2+ and K+ channels. Experimental evidence for the presence of nAChR antagonists and voltage-gated ionic channel blockers in venoms of Viperidae snakes is very scarce. In this study, effects of crude venoms of seven snake species (Vipera nikolskii, Echis multisquamatus, Gloydius saxatilis, Bitis arietans, Vipera renardi, Vipera lebetina, and Naja kaouthia) on nAChRs and voltage-gated Ca2+ channels were studied for the first time. The experiments were carried out on isolated identified neurons of the fresh-water mollusc Lymnaea stagnalis using voltage-clamp and intracellular perfusion techniques. All Viperidae snake venoms under study blocked nAChRs and voltage-gated Ca2+ channels. The potency of these venoms against nAChRs was significantly lower in comparison with N. kaouthia venom which is rich of α-neurotoxins; however, the extent of Ca2+ channel block by venoms of Viperidae snakes and N. kaouthia was similar. The data obtained suggest that Viperidae snake venoms tested in this study contain peptides with affinity both for nAChRs and for voltage-gated Ca2+ channels.

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References

  1. Servent, D., Winckler-Dietrich, V., Hu, H.Y., Kessler, P., Drevet, P., Bertrand, D., and Menez, A., Only Snake Curaremimetic Toxins with a Fifth Disulfide Bond Have High Affinity for the Neuronal oc7 Nicotinic Receptor, J. Biol. Chem., 1997, vol. 272, pp. 24279–24286.

    Article  CAS  Google Scholar 

  2. Tsetlin, V., Snake Venom Alfa-Neurotoxins and Other “Three-Finger” Proteins, Eur. J. Biochem., 1999, vol. 264, pp. 281–286.

    Article  CAS  Google Scholar 

  3. Tsetlin, V.I. and Hucho, F., Snake and Snail Toxins Acting on Nicotinic Acetylcholine Receptors: Fundamental Aspects and Medical Applications, FEES Lett., 2004, vol. 557, pp. 9–13.

    Article  CAS  Google Scholar 

  4. De Weille, J.R., Schweitz, H., Maes, P., Tartar, A., and 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, vol. 88, pp. 2437–2440.

    Article  Google Scholar 

  5. Watanabe, T.X., Itahara, Y., Kuroda, H., Chen, Y.N., Kimura, T., and Sakakibara, S., Smooth Muscle Relaxing and Hypotensive Activities of Synthetic Calciseptine and the Homologous Snake Venom Peptide FS [2], Jpn. J. Pharmacol., 1995, vol. 68, pp. 305–313.

    Article  CAS  Google Scholar 

  6. Imanishi, T., Matsushima, K., Kawaguchi, A., Wada, T., Yoshida, S., and Ichida, S., Increased Response to High KCl-Induced Elevation in the Intracellular Ca2+ Concentration in Differentiated NG108-15 Cells and the Inhibitory Effect of the L-Type Ca 2, Channel Blocker, Calciseptine, Neurochem. Res., 2006, vol. 31, pp. 33–40.

    CAS  PubMed  Google Scholar 

  7. Doorty, K.B., Bevan, S., Wadsworth, J.D.F., and Strong, P.N., A Novel Small Conductance Ca2+ Activated K+-Channel Blocker from Oxyuranus scutellatus Taipan Venom: Re-evaluation of Taicatoxin as a Selective Ca2+ Channel Probe, J. Biol. Chem., 1997, vol. 272, pp. 19 925–19 930.

    Article  CAS  Google Scholar 

  8. Wang, J., Shen, B., Guo, M., Lou, X., Duan, Y., Cheng, X.P., Teng, M., Niu, L., Liu, Q., Huang, Q., and Hao, Q., Blocking Effect and Crystal Structure of Natrin Toxin, a Cysteine-Rich Secretory Protein from Naja atra Venom that Targets the BKca Channel, Biochemistry, 2005, vol. 44, pp. 10145–10152.

    Article  CAS  Google Scholar 

  9. Hamilton, S.L., Yatani, A., Hawkes, M.J., Redding, K., and Brown, A.M., Atrotoxin: A Specific Agonist for Calcium Currents in Heart, Science, 1985, vol. 229, pp. 182–184.

    Article  CAS  Google Scholar 

  10. Yamazaki, Y., Koike, H., Sugiyama, Y., Motoyoshi, K., Wada, T., Hishinuma, S., Mita, M., and Morita, T., Cloning and Characterization of Novel Snake Venom Proteins that Block Smooth Muscle Contraction, Eur. J. Biochem., 2002, vol. 269, pp. 2708–2715.

    Article  CAS  Google Scholar 

  11. Schmidt, J.J., Weinstein, S.A., and Smith, L.A., Molecular Properties and Structure-Function Relationships of Lethal Peptides from Venom of Wagler's Pit Viper, Trim eresurus wagleri, Toxicon, 1992, vol. 30, pp. 1027–1036.

    CAS  Google Scholar 

  12. Vulfius, C.A., Krasts, I.V., Utkin, Yu.N., and Tsetlin, V.I., Nicotinic Receptors in Lymnaea stagnalis Neurons Are Blocked by (x-Neurotoxins from Cobra Venoms, Neurosci. Lett., 2001, vol. 309, pp. 189–192.

    Article  CAS  Google Scholar 

  13. Vulfius, C.A., Tumina, O.B., Kasheverov, I.E., Utkin, Yu.N., and Tsetlin, V.I., Diversity of Nicotinic Receptors Mediating Cl- Current in Lymnaea Neurons Distinguished with Specific Agonists and Antagonist, Neurosci. Lett., 2005, vol. 373, pp. 232–236.

    Article  CAS  Google Scholar 

  14. Kislov, A.N. and Kazachenko, V.N., Ion Current of Excited Cholinergic Membrane of the Giant Isolated Snail Neurones, Biofizika zhivoi kletki (Biophysics of a Living Cell), Frank, G.M., Ed., vol. 4., Pushchino, 1974, pp. 39–44.

    Google Scholar 

  15. Gorbacheva, E.V., Vulfius, C.A., Kasheverov, I.E., Zhmak, M.N., Utkin, Yu.N., and Tsetlin, V.I., Characterization of Nicotinic Acetylcholine Receptors in Lymnaea stagnalis Neurons by Ionic Selectivity and Sensitivity to Specific oc-Conotoxins, International Congress “Neuroscience for Medicine and Psychology,” Sudak, 2006, p. 81.

    Google Scholar 

  16. Van Nierop, P., Keramidas, A., Bertrand, S., Van Minnen, J., Gouwenberg, Y., Bertrand, D., and Smit, A.B., Identification of Molluscan Nicotinic Acetylcholine Receptor (NAchR) Subunits Involved in Formation of Cation- and Anion-Selective nAChRs, J. Neurosci., 2005, vol. 25, pp. 10617–10626.

    Article  Google Scholar 

  17. Van Nierop, P., Bertrand, S., Munno, D.W., Gouwenberg, Y., Van Minnen, J., Spafford, J.D., Syed, N.I., Bertrand, D., and Smit, A.B., Identification and Functional Expression of a Family of Nicotinic Acetylcholine Receptor Subunits in the Central Nervous System of the Mollusc Lymnaea stagnalis, J. Biol. Chem., 2006, vol. 281, pp. 1680–1691.

    Article  Google Scholar 

  18. Spafford, J.D., Munno, D.W., Van Nierop, P., Feng, Z.P., Jarvis, S.E., Gallin, W.J., Smit, A.B., Zamponi, G.W., and Syed, N.I., Calcium Channel Structural Determi nants of Synaptic Transmission between Identified Invertebrate Neurons, J. Biol. Chem., 2003, vol. 278, pp. 4258–4267.

    Article  CAS  Google Scholar 

  19. Kasheverov, I.E., Zhmak, M.N., Vulfius, C.A., Gorbacheva, E.X., Mordvintsev, D.Y., Utkin, Y.N., Van Elk, R., Smit, A.B., and Tsetlin, V.I., α-Conotoxin Analogs with Additional Positive Charge Show Increased Selectivity towards Torpedo californica and Some Neuronal Subtypes of Nicotinic Acetylcholine Receptors, FEES Journal, 2006, vol. 273, pp. 4470–4481.

    CAS  Google Scholar 

  20. Rossetto, O., Morbiato, L., Caccin, P., Rigoni, M., and Montecucco, C., Presynaptic Enzymatic Neurotoxins, J. Neurochem., 2006, vol. 97, pp. 1534–1545.

    Article  CAS  Google Scholar 

  21. Yamazaki, Y and Morita, T., Structure and Function of Snake Venom Cysteine-Rich Secretory Proteins, Toxicon, 2004, vol. 44, pp. 227–231.

    Article  CAS  Google Scholar 

  22. McArdle, J.J., Lentz, T.L., Witzemann, V., Schwarz, H., Weinstein, S.A., and Schmidt, J.J., Waglerin-1 Selectively Blocks the Epsilon Form of the Muscle Nicotinic Acetylcholine Receptor, J Pharmacol. Exp. Ther, 1999, vol. 289, pp. 543–550.

    CAS  PubMed  Google Scholar 

  23. Junqueira-de-Azevedo, I.L., Ching, A.T., Carvalho, E., Faria, F., Nishiyama, M.Y., Jr., Ho, P.L., and Diniz, M.R., Lachesis muta (Viperidae) cDNAs Reveal Diverging Pit Viper Molecules and Scaffolds Typical of Cobra (Elapidae) Venoms: Implications for Snake Toxin Repertoire Evolution, Genetics, 2006, vol. 173, pp. 877–889.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, Institutskaya ul. 3, Pushchino, Moscow oblast, 142290, Russia

    E. V. Gorbacheva & C. A. Vulfius

  2. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia

    V. G. Starkov, V. I. Tsetlin & Yu. N. Utkin

Authors
  1. E. V. Gorbacheva
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  2. V. G. Starkov
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  3. V. I. Tsetlin
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  4. Yu. N. Utkin
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  5. C. A. Vulfius
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Correspondence to E. V. Gorbacheva.

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Original Russian Text © E.V. Gorbacheva, V.G. Starkov, V.I. Tsetlin, Yu.N. Utkin, C.A. Vulfius, 2008, published in Biologicheskie Membrany, 2008, Vol. 25, No. 2, pp. 122–127.

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Gorbacheva, E.V., Starkov, V.G., Tsetlin, V.I. et al. Viperidae snake venoms block nicotinic acetylcholine receptors and voltage-gated Ca2+ channels in identified neurons of fresh-water snail Lymnaea stagnalis. Biochem. Moscow Suppl. Ser. A 2, 14–18 (2008). https://doi.org/10.1134/S1990747808010030

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  • DOI: https://doi.org/10.1134/S1990747808010030

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