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Sodium Channel Toxins and Neurotransmitter Release

Neurochemical Research volume 28, pages 1607–1611 (2003)Cite this article

Abstract

Voltage-dependent sodium channels (VDSC) are an important class of ion channels in excitable cells, where they are responsible for the generation and conduction of action potential. In addition, the release of neurotransmitters from nerve terminals is influenced by sodium channel activity. The function of VDSC is subject to modulation by various neurotoxins, such as scorpion toxins, which have long been used as tools in the investigation of neurotransmitter release. This opens an interesting perspective concerning modulation of neurotransmission via pharmacological manipulation of sodium channel properties, which can lead to a better understanding of their physiological and pathological roles. Here we briefly review the studies of neurotoxins acting on sodium channels, focusing primarily on the view of the mechanisms of neurotransmitter release.

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References

  1. Llinas, R. R. 1988. The intrinsic electrophysiological properties of mammalian neurons: Insights into central nervous-system function. Science 242:1654-1664.

    PubMed  Google Scholar 

  2. Taylor, C. P. 1993. Na+ currents that fail to inactivate. Trends Neurosci. 16:455-460.

    PubMed  Google Scholar 

  3. Crill, W. E. 1996. Persistent sodium current in mammalian central neurons. Annu. Rev. Physiol. 58:349-362.

    PubMed  Google Scholar 

  4. Petrecca, K., Amellal, F., Laird, D. W., Cohen, S. A., and Shrier, A. 1997. Sodium channel distribution within the rabbit atrioventricular node as analysed by confocal microscopy. J. Physiol. 501(Pt. 2): 263-274.

    PubMed  Google Scholar 

  5. Safronov, B. V., Wolff, M., and Vogel, W. 1997. Functional distribution of three types of Na+ channel on soma and processes of dorsal horn neurones of rat spinal cord. J. Physiol. 503(Pt. 2): 371-385.

    PubMed  Google Scholar 

  6. Alessandri-Haber, N., Paillart, C., Arsac, C., Gola, M., Couraud, F., and Crest, M. 1999. Specific distribution of sodium channels in axons of rat embryo spinal motoneurones. J. Physiol. 518(Pt. 1): 203-214.

    PubMed  Google Scholar 

  7. Bouron, A. and Reuter, H. 1996. A role of intracellular Na+ in the regulation of synaptic transmission and turnover of the vesicular pool in cultured hippocampal cells. Neuron 17:969-978.

    PubMed  Google Scholar 

  8. Cantrell, A. R., Smith, R. D., Goldin, A. L., Scheuer, T., and Catterall, W. A. 1997. Dopaminergic modulation of sodium current in hippocampal neurons via cAMP-dependent phosphorylation of specific sites in the sodium channel alpha subunit. J. Neurosci. 17:7330-7338.

    PubMed  Google Scholar 

  9. Westenbroek, R. E., Merrick, D. K., and Catterall, W. A. 1989. Differential subcellular localization of the RI and RII Na+ channel subtypes in central neurons. Neuron 3:695-704.

    PubMed  Google Scholar 

  10. Felts, P. A., Yokoyama, S., Dib-Hajj, S., Black, J. A., and Waxman, S. G. 1997. Sodium channel alpha-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1): Different expression patterns in developing rat nervous system. Brain Res. Mol. Brain Res. 45:71-82.

    PubMed  Google Scholar 

  11. Beckh, S., Noda, M., Lubbert, H., and Numa, S. 1989. Differential regulation of three sodium channel messenger RNAs in the rat central nervous system during development. EMBO J. 8:3611-3616.

    PubMed  Google Scholar 

  12. Beckh, S. 1990. Differential expression of sodium channel mRNAs in rat peripheral nervous system and innervated tissues. FEBS Lett. 262:317-322.

    PubMed  Google Scholar 

  13. Black, J. A., Yokoyama, S., Higashida, H., Ransom, B. R., and Waxman, S. G. 1994. Sodium channel mRNAs I, II and III in the CNS: Cell-specific expression. Brain Res. Mol. Brain Res. 22:275-289.

    PubMed  Google Scholar 

  14. Schaller, K. L., Krzemien, D. M., Yarowsky, P. J., Krueger, B. K., and Caldwell, J. H. 1995. A novel, abundant sodium channel expressed in neurons and glia. J. Neurosci. 15:3231-3242.

    Google Scholar 

  15. Cestele, S. and Catterall, W. A. 2000. Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie 82:883-892.

    PubMed  Google Scholar 

  16. Goldin, A. L., Barchi, R. L., Caldwell, J. H., Hofmann, F., Howe, J. R., Hunter, J. C., Kallen, R. G., Mandel, G., Meisler, M. H., Netter, Y. B., Noda, M., Tamkun, M. M., Waxman, S. G., Wood, J. N., and Catterall, W. A. 2000. Nomenclature of voltage-gated sodium channels. Neuron 28:365-368.

    PubMed  Google Scholar 

  17. Noda, M., Ikeda, T., Suzuki, H., Takeshima, H., Takahashi, T., Kuno, M., and Numa, S. 1986. Expression of functional sodium channels from cloned cDNA. Nature 322:826-828.

    PubMed  Google Scholar 

  18. Auld, V. J., Goldin, A. J., Krafte, D. S., Marshall, J., Dunn, J. M., Catterall, W. A., Lester, H. A., Davidson, N., and Dunn, R. J. 1988. A rat brain Na+ channel alpha subunit with novel gating properties. Neuron 1:449-461.

    PubMed  Google Scholar 

  19. Kayano, T., Noda, M., Flockerzi, V., Takahashi, H., and Numa, S. 1988. Primary structure of rat brain sodium channel III deduced from the cDNA sequence. FEBS Lett. 228:187-194.

    PubMed  Google Scholar 

  20. Urenjak, J. and Obrenovitch, T. P. 1996. Pharmacological modulation of voltage-gated Na+ channels: A rational and effective strategy against ischemic drain damage. Pharmacol. Rev. 48:21-67.

    PubMed  Google Scholar 

  21. Gautron, S., Dossantos, G., Pintohenrique, D., Koulakoff, A., Gros, F., and Berwaldnetter, Y. 1992. The glial voltage-gated sodium channel: Cell-and tissue-specific mRNA expression. Proc. Nat. Acad. Sci. USA 89:7272-7276.

    PubMed  Google Scholar 

  22. Hille, B., Ritchie, J. M., and Strichartz, G. R. 1975. The effect of surface charge on the nerve membrane on the action of tetrodotoxin and saxitoxin in frog myelinated nerve. J. Physiol. 250:34P-35P.

    PubMed  Google Scholar 

  23. Hille, B. 1975. The receptor for tetrodotoxin and saxitoxin: A structural hypothesis. Biophys. J. 15:615-619.

    PubMed  Google Scholar 

  24. Narahashi, T., Anderson, N. C., and Moore, J. W. 1966. Tetrodotoxin does not block excitation from inside the nerve membrane. Science 153:765-767.

    PubMed  Google Scholar 

  25. Narahashi, T. 1972. Mechanism of action of tetrodotoxin and saxitoxin on excitable membranes. Fed. Proc. 31:1124-1132.

    PubMed  Google Scholar 

  26. Ulbricht, W. 1998. Effects of veratridine on sodium currents and fluxes. Rev. Physiol Biochem. Pharmacol. 133:1-54.

    PubMed  Google Scholar 

  27. Catterall, W. A. 1992. Cellular and molecular biology of voltage-gated sodium channels. Physiol. Rev. 72:S15-S48.

    PubMed  Google Scholar 

  28. Vijverberg, H. P., Pauron, D., and Lazdunski, M. 1984. The effect of Tityus serrulatus scorpion toxin gamma on Na channels in neuroblastoma cells. Pflugers Arch. 401:297-303.

    PubMed  Google Scholar 

  29. Lombet, A., Bidard, J. N., and Lazdunski, M. 1987. Ciguatoxin and brevetoxins share a common receptor site on the neuronal voltage-dependent Na+ channel. FEBS Lett. 219:355-359.

    PubMed  Google Scholar 

  30. Hasson, A., Fainzilber, M., Gordon, D., Zlotkin, E., and Spira, M. E. 1993. Alteration of sodium currents by new peptide toxins from the venom of a molluscivorous Conus Snail. Eur. J. Neurosci. 5:56-64.

    PubMed  Google Scholar 

  31. Noda, M., Suzuki, H., Numa, S., and Stuhmer, W. 1989. A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II. FEBS Lett. 259:213-216.

    PubMed  Google Scholar 

  32. Rogers, J. C., Qu, Y., Tanada, T. N., Scheuer, T., and Catterall, W. A. 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. 271:15950-15962.

    PubMed  Google Scholar 

  33. Trainer, V. L., Baden, D. G., and Catterall, W. A. 1994. Identification of peptide components of the brevetoxin receptor site of rat brain sodium channels. J. Biol. Chem. 269:19904-19909.

    PubMed  Google Scholar 

  34. Romano-Silva, M. A., Ribeiro-Santos, R., Gomez, M. V., Moraes-Santos, T., and Brammer, M. J. 1994. Tityustoxin-mediated Na+ influx is more efficient than KCl depolarization in promoting Ca2+-dependent glutamate release from synaptosomes. Neurosci. Lett. 169:90-92.

    PubMed  Google Scholar 

  35. Gomez, R. S., Casali, T. A. A., Romano-Silva, M. A., Cordeiro, M. N., Diniz, C. R., Moraes-Santos, T., Prado, M. A. M., and Gomez, M. V. 1995. The effect of Phtx(3) on the release of H-3 acetylcholine induced by tityustoxin and potassium in brain cortical slices and myenteric plexus. Neurosci. Lett. 196:131-133.

    PubMed  Google Scholar 

  36. Stier, C., Skorka, G., Sohr, R., and Ott, T. 1996. Time course and role of extracellular Ca2+ in veratridine-induced glutamate release. Neuroreport 7:401-404.

    PubMed  Google Scholar 

  37. Conceicao, I. M., Lebrun, I., Cano-Abad, M., Gandia, L., Hernandez-Guijo, J. M., Lopez, M. G., Villarroya, M., Jurkiewicz, A., and Garcia, A. G. 1998. Synergism between toxin-gamma from Brazilian scorpion Tityus serrulatus and veratridine in chromaffin cells. Am. J. Physiol. 274:C1745-C1754.

    PubMed  Google Scholar 

  38. do Nascimento, J. L., Ventura, A. L., and Paes, D. C. 1998. Veratridine-and glutamate-induced release of [3H]-GABA from cultured chick retina cells: Possible involvement of a GAT-1-like subtype of GABA transporter. Brain Res. 798:217-222.

    PubMed  Google Scholar 

  39. Halmosa, G., Gaborjan, A., Lendvai, B., Repassy, G., Szabo, L. Z., and Vizi, E. S. 2000. Veratridine-evoked release of dopamine from guinea pig isolated cochlea. Hear. Res. 144:89-96.

    PubMed  Google Scholar 

  40. Fernandes, V. M. V., Nicolato, R., Moraes-Santos, T., Gomez, R. S., Prado, M. A. M., Romano-Silva, M. A., and Gomez, M. V. 2001. Beta-scorpion toxin induces the release of gamma-3 [H-3] aminobutyric acid in rat brain slices. Neuroreport 12:2911-2913.

    PubMed  Google Scholar 

  41. Nicolato, R., Fernandes, V. M., Moraes-Santos, T., Gomez, R. S., Prado, M. A., Romano-Silva, M. A., and Gomez, M. V. 2002. Release of gamma-[(3)H]aminobutyric acid in rat brain cortical slices by alpha-scorpion toxin. Neurosci. Lett. 325:155-158.

    PubMed  Google Scholar 

  42. Basudev, H., Romano-Silva, M. A., Brammer, M. J., and Campbell, I. C. 1995. Effects of sodium on PKC translocation: Relationship to neurotransmitter release. Neuroreport 6:809-812.

    PubMed  Google Scholar 

  43. Romano-Silva, M. A., Ribeiro-Santos, R., Ribeiro, A. M., Gomez, M. V., Diniz, C. R., Cordeiro, M. N., and Brammer, M. J. 1993. Rat cortical synaptosomes have more than one mechanism for Ca2+ entry linked to rapid glutamate release: Studies using the Phoneutria nigriventer toxin PhTX2 and potassium depolarization. Biochem. J. 296(Pt. 2): 313-319.

    PubMed  Google Scholar 

  44. Massensini, A. R., Moraes-Santos, T., Gomez, M. V., and Romano-Silva, M. A. 1998. Alpha-and beta-scorpion toxins evoke glutamate release from rat cortical synaptosomes with different effects on [Na+]i and [Ca2+]i. Neuropharmacology 37:289-297.

    PubMed  Google Scholar 

  45. Bicalho, A. F., Guatimosim, C., Prado, M. A., Gomez, M. V., and Romano-Silva, M. A. 2002. Investigation of the modulation of glutamate release by sodium channels using neurotoxins. Neuroscience 113:115-123.

    PubMed  Google Scholar 

  46. Warnick, J. E., Albuquerque, E. X., and Diniz, C. R. 1976. Electrophysiological observations on the action of the purified scorpion venom, tityustoxin, on nerve and skeletal muscle of the rat. J. Pharmacol. Exp. Ther. 198:155-167.

    PubMed  Google Scholar 

  47. Gomez, M. V., Diniz, C. R., and Barbosa, T. S. 1975. Comparison of effects of scorpion-venom tityustoxin and ouabain on release of acetylcholine from incubated slices of rat-brain. J. Neurochem. 24:331-336.

    PubMed  Google Scholar 

  48. Casali, T. A. A., Gomez, R. S., Moraes-Santos, T., and Gomez, M. V. 1995. Differential effects of calcium-channel antagonists on tityustoxin and ouabain-induced release of [H-3] acetylcholine from brain cortical slices. Neuropharmacology 34:599-603.

    PubMed  Google Scholar 

  49. Massensini, A. R., Romano-Silva, M. A., Gomez, M. V., and Moraes-Santos, T. 1998. Tityustoxin and toxin-gamma: A comparative study of their effects on acetylcholine release from rat brain cortical slices. Med. Sci. Res. 26:583-584.

    Google Scholar 

  50. Romano-Silva, M. A., Gomez, M. V. and Brammer, M. J. 1994. Modulation of Ca2+-Stimulated glutamate release from synaptosomes by Na+ entry through tetrodotoxin-sensitive channels. Biochem. J. 304:353-357.

    PubMed  Google Scholar 

  51. Catterall, W. A. and Gainer, M. 1985. Interaction of brevetoxin A with a new receptor site on the sodium channel. Toxicon 23:497-504.

    PubMed  Google Scholar 

  52. Berman, F. W. and Murray, T. F. 1999. Brevetoxins cause acute excitotoxicity in primary cultures of rat cerebellar granule neurons. J. Pharmacol. Exp. Ther. 290:439-444.

    PubMed  Google Scholar 

  53. Meunier, F. A., Colasante, C., and Molgo, J. 1997. Sodium-dependent increase in quantal secretion induced by brevetoxin-3 in Ca2+-free medium is associated with depletion of synaptic vesicles and swelling of motor nerve terminals in situ. Neuroscience 78:883-893.

    PubMed  Google Scholar 

  54. Catterall, W. A. 1980. Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. Annu. Rev. Pharmacol. Toxicol. 20:15-43.

    PubMed  Google Scholar 

  55. Sosa, M. A. and Zengel, J. E. 1993. Use of mu-conotoxin GIIIA for the study of synaptic transmission at the frog neuromuscular junction. Neurosci. Lett. 157:235-238.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Departamento de Fisiologia e Biofisica, Núcleo de Neurociências, ???

    André Ricardo Massensini

  2. Laboratório de Neurofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Carlos 6627, Belo, Horizonte-MG, Brazil

    Marco Aurélio Romano-Silva & Marcus Vinícius Gomez

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  1. André Ricardo Massensini
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  2. Marco Aurélio Romano-Silva
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  3. Marcus Vinícius Gomez
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Correspondence to Marcus Vinícius Gomez.

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Massensini, A.R., Romano-Silva, M.A. & Gomez, M.V. Sodium Channel Toxins and Neurotransmitter Release. Neurochem Res 28, 1607–1611 (2003). https://doi.org/10.1023/A:1025643030044

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  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1025643030044

  • Sodium channels
  • scorpion toxins
  • tityustoxin
  • veratridine
  • neurotransmission