Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1976 Nov;73(11):4055–4059. doi: 10.1073/pnas.73.11.4055

Sea anemone toxin:a tool to study molecular mechanisms of nerve conduction and excitation-secretion coupling.

G Romey, J P Abita, H Schweitz, G Wunderer, Lazdunski
PMCID: PMC431325  PMID: 1087023

Abstract

The effects of polypeptide neurotoxin from Anemonia sulcata on nerve conduction in crayfish giant axons and on frog myelinated fibers have been analyzed. The main features of toxin action are the following: (i) the toxin acts at very low doses and its action is apparently irreversible. (ii) The toxin selectively affects the closing (inactivation) of the Na+ channel by slowing it down considerably; it does not alter the opening mechanism of the Na+ channel or the steady-state potassium conductance. (iii) The tetrodotoxin-receptor association is unaffected by previous treatment of the axonal membrane with the sea anemone toxin. (iv) Conversely, the sea anemone toxin can only associate with the membrane when the Na+ channel is open for Na+; it does not bind when the channel is previously blocked by tetrodotoxin. (v) Besides its effect on the action potential, the sea anemone toxin displays a veratridine-type depolarizing action at low Ca2+ concentration which can be suppressed by tetrodotoxin. The sea anemone toxin greatly stimulates the release of gamma-[3H]aminobutyric acid from neurotransmitter-loaded rat brain synaptosomes. The apparent dissociation constant of the neurotoxin-receptor complex in this system is 20 nM. The sea anemone toxin effect is antagonized by tetrodotoxin.

Full text

PDF
4055

Images in this article

4056Image
on p.4056
4056Image
on p.4056
4056Image
on p.4056
4056Image
on p.4056
4057Image
on p.4057
4058Image
on p.4058
4058Image
on p.4058
4058Image
on p.4058

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albuquerque E. X., Daly J. W., Witkop B. Batrachotoxin: chemistry and pharmacology. Science. 1971 Jun 4;172(3987):995–1002. doi: 10.1126/science.172.3987.995. [DOI] [PubMed] [Google Scholar]
  2. Balerna M., Fosset M., Chicheportiche R., Romey G., Lazdunski M. Constitution and properties of axonal membranes of crustacean nerves. Biochemistry. 1975 Dec 16;14(25):5500–5511. doi: 10.1021/bi00696a019. [DOI] [PubMed] [Google Scholar]
  3. Benzer T. I., Raftery M. A. Partial characterization of a tetrodotoxin-binding component from nerve membrane. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3634–3637. doi: 10.1073/pnas.69.12.3634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blaustein M. P. Effects of potassium, veratridine, and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro. J Physiol. 1975 Jun;247(3):617–655. doi: 10.1113/jphysiol.1975.sp010950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Béress L., Béress R. Purification of three polypeptides with neuro- and cardiotoxic activity from the sea anemone Anemonia sulcata. Toxicon. 1975 Nov;13(5):359–367. doi: 10.1016/0041-0101(75)90196-8. [DOI] [PubMed] [Google Scholar]
  6. Béress L., Béress R., Wunderer G. Isolation and characterisation of three polypeptides with neurotoxic activity from Anemonia sulcata. FEBS Lett. 1975 Feb 15;50(3):311–314. doi: 10.1016/0014-5793(75)80517-5. [DOI] [PubMed] [Google Scholar]
  7. Catterall W. A. Activation of the action potential Na+ ionophore of cultured neuroblastoma cells by veratridine and batrachotoxin. J Biol Chem. 1975 Jun 10;250(11):4053–4059. [PubMed] [Google Scholar]
  8. Chicheportiche R., Vincent J. P., Kopeyan C., Schweitz H., Lazdunski M. Structure-function relationship in the binding of snake neurotoxins to the torpedo membrane receptor. Biochemistry. 1975 May 20;14(10):2081–2091. doi: 10.1021/bi00681a007. [DOI] [PubMed] [Google Scholar]
  9. Colquhoun D., Henderson R., Ritchie J. M. The binding of labelled tetrodotoxin to non-myelinated nerve fibres. J Physiol. 1972 Dec;227(1):95–126. doi: 10.1113/jphysiol.1972.sp010022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cotman C. W., Haycock J. W., White W. F. Stimulus-secretion coupling processes in brain: analysis of noradrenaline and gamma-aminobutyric acid release. J Physiol. 1976 Jan;254(2):475–505. doi: 10.1113/jphysiol.1976.sp011241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Evans M. H. Tetrodotoxin, saxitoxin, and related substances: their applications in neurobiology. Int Rev Neurobiol. 1972;15:83–166. doi: 10.1016/s0074-7742(08)60329-3. [DOI] [PubMed] [Google Scholar]
  12. GRAY E. G., WHITTAKER V. P. The isolation of nerve endings from brain: an electron-microscopic study of cell fragments derived by homogenization and centrifugation. J Anat. 1962 Jan;96:79–88. [PMC free article] [PubMed] [Google Scholar]
  13. Henderson R., Wang J. H. Solubilization of a specific tetrodotoxin-binding component from garfish olfactory nerve membrane. Biochemistry. 1972 Nov 21;11(24):4565–4569. doi: 10.1021/bi00774a022. [DOI] [PubMed] [Google Scholar]
  14. Hille B. Ionic channels in nerve membranes. Prog Biophys Mol Biol. 1970;21:1–32. doi: 10.1016/0079-6107(70)90022-2. [DOI] [PubMed] [Google Scholar]
  15. Katz B., Miledi R. Further study of the role of calcium in synaptic transmission. J Physiol. 1970 May;207(3):789–801. doi: 10.1113/jphysiol.1970.sp009095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Katz B., Miledi R. The effect of prolonged depolarization on synaptic transfer in the stellate ganglion of the squid. J Physiol. 1971 Jul;216(2):503–512. doi: 10.1113/jphysiol.1971.sp009537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koppenhöfer E., Schmidt H. Die Wirkung von Skorpiongift auf die Ionenströme des Ranvierschen Schnürrings. I. Die Permeabilitäten PNa und PK. Pflugers Arch. 1968;303(2):133–149. doi: 10.1007/BF00592631. [DOI] [PubMed] [Google Scholar]
  18. Levy W. B., Haycock J. W., Cotman C. W. Effects of polyvalent cations on stimulus-coupled secretion of (14C)-gamma-aminobutyric acid from isolated brain synaptosomes. Mol Pharmacol. 1974 May;10(3):438–449. [PubMed] [Google Scholar]
  19. Narahashi T. Chemicals as tools in the study of excitable membranes. Physiol Rev. 1974 Oct;54(4):813–889. doi: 10.1152/physrev.1974.54.4.813. [DOI] [PubMed] [Google Scholar]
  20. Narahashi T., Moore J. W., Shapiro B. I. Condylactis toxin: interaction with nerve membrane ionic conductances. Science. 1969 Feb 14;163(3868):680–681. doi: 10.1126/science.163.3868.680. [DOI] [PubMed] [Google Scholar]
  21. Narahashi T., Shapiro B. I., Deguchi T., Scuka M., Wang C. M. Effects of scorpion venom on squid axon membranes. Am J Physiol. 1972 Apr;222(4):850–857. doi: 10.1152/ajplegacy.1972.222.4.850. [DOI] [PubMed] [Google Scholar]
  22. Nonner W. A new voltage clamp method for Ranvier nodes. Pflugers Arch. 1969;309(2):176–192. doi: 10.1007/BF00586967. [DOI] [PubMed] [Google Scholar]
  23. Ota M., Narahashi T., Keeler R. F. Effects of veratrum alkaloids on membrane potential and conductance of squid and crayfish giant axons. J Pharmacol Exp Ther. 1973 Jan;184(1):143–154. [PubMed] [Google Scholar]
  24. Rathmayer W., Jessen B. Effect of toxins of sea anemones on neuromuscular transmission. Naturwissenschaften. 1975 Nov;62(11):538–539. doi: 10.1007/BF00609079. [DOI] [PubMed] [Google Scholar]
  25. Romey G., Chicheportiche R., Lazdunski M., Rochat H., Miranda F., Lissitzky S. Scorpion neurotoxin - a presynaptic toxin which affects both Na+ and K+ channels in axons. Biochem Biophys Res Commun. 1975 May 5;64(1):115–121. doi: 10.1016/0006-291x(75)90226-0. [DOI] [PubMed] [Google Scholar]
  26. Shapiro B. I. Purification of a toxin from tentacles of the anemone Condylactis gigantea. Toxicon. 1968 May;5(4):253–259. doi: 10.1016/0041-0101(68)90115-3. [DOI] [PubMed] [Google Scholar]
  27. Ulbricht W. The effect of veratridine on excitable membranes of nerve and muscle. Ergeb Physiol. 1969;61:18–71. doi: 10.1007/BFb0111446. [DOI] [PubMed] [Google Scholar]
  28. Weber M., Changeux J. P. Binding of Naja nigricollis (3H)alpha-toxin to membrane fragments from Electrophorus and Torpedo electric organs. I. Binding of the tritiated alpha-neurotoxin in the absence of effector. Mol Pharmacol. 1974 Jan;10(1):1–14. [PubMed] [Google Scholar]
  29. Wunderer G., Machleidt W., Wachter E. Toxin II from Anemonia sulcata-the first sequence of a coelenterate toxin. Hoppe Seylers Z Physiol Chem. 1976 Feb;357(2):239–240. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES