Skip to main content

Factors Underlying the Characteristic Inhibition of the Neuronal Release of Transmitters by Tetanus and Various Botulinum Toxins

  • Chapter
Botulinum and Tetanus Neurotoxins

Abstract

Although the gross structures of all serotypes of botulinum neurotoxin (BoNT) and tetanus toxin (TeTX) are similar — proteins composed of a disulphide-linked heavy chain (H; Mr ~ 100 kDa) and light chain (L; Mr ~ 50 kDa) — dissimilarities exist in their amino acid sequences 1, 2, 3. Each of the BoNT types produce flaccid neuromuscular paralysis due to a preferential inhibition of acetylcholine (ACh) release from peripheral nerves whilst TeTX gives rise to a spastic paralysis resulting from a blockade of inhibitory transmitter release at central synapses4. However, it is intriguing that characteristics of the neuroparalysis caused by type A BoNT differ from those of all the other serotypes and TeTX, the latter exhibiting many common features at motor nerve terminals5. For example, asynchronous release can be elicited by intense neural stimulation of muscle endplates treated with TeTX6, 7 or BoNT/B8, /D9, /E10 (but see 11) whilst tissue incubated with BoNT/A yield detectable levels of synchronous release. Furthermore, double-poisoning experiments revealed that BoNT/A is unable to alter the pattern of inhibition already produced by type B or TeTX. Moreover, elevation of the intracellular Ca2+ concentration (using 4-aminopyridine [4-AP]8, 12, 13, 14 or black widow spider venom15, 16, 17 ) overcomes (at least temporarily) the blockade of the quantal release of ACh caused by limited exposure to BoNT/A (see later) whereas much less extensive reversal of poisoning by any of these other toxins 8, 17 and F 18 is seen. Such notable differences have also been reported 19 for central nerve terminals in terms of a more pronounced reversal of the action of BoNT/A relative to B using the Ca2+ ionophore, A23187; additionally, dissassembly of micro tubules antagonised the ability of type B (but not A) to reduce catecholamine release. Data is presented in this chapter showing that the microtubule involvement also applies to other transmitters and is also the case for TeTX and BoNT/E or /F; the importance of the cytoskeletal elements in secretion and involvement with the action of the latter toxins is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. U. Eisel, W. Jarausch, K. Goretzki, A. Henschen, J. Engels, U. Weller, M. Hudel, E. Habermann, and H. Niemann, Tetanus toxin: primary structure, expression in E.coli, and homology with botulinum toxins, EMBO J. 5: 2495–2502 (1986).

    PubMed  CAS  Google Scholar 

  2. H. Niemann, Molecular biology of Clostridial toxins, in: “Sourcebook of Bacterial Protein Toxins,” J. Alouf and J. Freer ed., Academic Press, London (1991).

    Google Scholar 

  3. D. E. Thompson, J. K. Brehm, J. D. Oultram, T.-L. Swinfield, C. C. Shone, T. Atkinson, J. Melling, and N. P. Minton, The complete amino acid sequence of the Clostridium botulinum type A neurotoxin deduced by nucleotide sequence analysis of the encoding gene, Eur.J.Biochem. 189: 73–81 (1990).

    Article  PubMed  CAS  Google Scholar 

  4. L. L. Simpson (ed.). “Botulinum Neurotoxin and Tetanus Toxin”, Academic Press, New York (1989).

    Google Scholar 

  5. J. O. Dolly, Peptide toxins that alter neurotransmitter release, in: “Handbook of Experimental Pharmacology, Vol. 102. Selective Neurotoxicity,” H. Herken and F. Hucho eds., Springer-Verlag, Berlin (1992).

    Google Scholar 

  6. F. Dreyer and A. Schmitt, Different effects of botulinum A toxin and tetanus toxin on the transmitter releasing process at the mammalian neuromuscular junction, Neuroscience Lett. 26: 307–311 (1981).

    Article  CAS  Google Scholar 

  7. F. Dreyer and A. Schmitt, Transmitter release in tetanus and botulinum A toxin-poisoned mammalian motor endplates and its dependence on nerve stimulation and temperature, Pflügers Archiv Eur.J.Physiol. 399: 228–234 (1983).

    Article  CAS  Google Scholar 

  8. M. Gansel, R. Penner, and F. Dreyer, Distinct sites of action of Clostridial neurotoxins revealed by double-poisoning of mouse motor nerve terminals, Pflugers Arch. 409: 533–539 (1987).

    Article  PubMed  CAS  Google Scholar 

  9. J. Molgó, L. S. Siegel, N. Tabti, and S. Thesleff, A study of synchronization of quantal transmitter release from mammalian motor endings by the use of botulinal toxins type A and D, J.Physiol. 411: 195–205 (1989).

    PubMed  Google Scholar 

  10. L. Wieszt and F. Dreyer, Mode of action of botulinum type E on the transmitter release process at the mouse neuromuscular junction, Naunyn-Schmeideberg’s Arch Pharmacol. 344 (suppl.): R74 (1991).

    Google Scholar 

  11. J. Molgó, B. R. DasGupta, and S. Thesleff, Characterization of the actions of botulinum neurotoxin type E at the rat neuromuscular junction, Acta Physiol Scand. 137: 497–501 (1989).

    Article  Google Scholar 

  12. L. C. Sellin, S. Thesleff, and B. R. DasGupta, Different effects of types A and B botulinum toxin on transmitter release at the rat neuromuscular junction, Acta Physiol.Scand. 119: 127–133 (1983).

    Article  PubMed  CAS  Google Scholar 

  13. L. S. Siegel, A. D. Johnson-Winegar, and L. C. Sellin, Effect of 3,4diaminopyridine on the survival of mice injected with botulinum neurotoxin type A, B, E, or F, Toxicol.appl. Pharmac. 84: 255 (1986).

    Article  CAS  Google Scholar 

  14. L. L. Simpson, Use of pharmacologic antagonists to deduce commonalities of biologic activity among Clostridial neurotoxins, J.Pharmacol.Exp.Ther. 245: 867–872 (1988).

    PubMed  CAS  Google Scholar 

  15. I. Kao, D. B. Drachman, and D. L. Price, Botulinum toxin: mechanism of presynaptic blockade, Science. 193: 1256–1258 (1976).

    Article  PubMed  CAS  Google Scholar 

  16. S. G. Cull-Candy, H. Lundh, and S. Thesleff, Effects of botulinum toxin on neuromuscular transmission in the rat, J.Physiol. 260: 177–203 (1976).

    PubMed  CAS  Google Scholar 

  17. F. Dreyer, F. Rosenberg, C. Becker, H. Bigalke, and R. Penner, Differential effects of various secretagogues on quantal transmitter release from mouse motor nerve terminals treated with botulinum A and tetanus toxin, Naunyn-Schmiedebergs Arch.Pharmacol. 335: 1–7 (1987).

    Article  PubMed  CAS  Google Scholar 

  18. J. A. Kauffman, J. F. Way, L. S. Siegel, and L. C. Sellin, Comparison of the action of types A and F botulinum toxin at the rat neuromuscular junction, Toxicol.Appl.Pharmaocol. 79: 211–217 (1985).

    Article  CAS  Google Scholar 

  19. A. C. Ashton and J. O. Dolly, Microtubule-dissociating drugs and A23187 reveal differences in the inhibition of synaptosomal transmitter release by botulinum neurotoxins type A and B., J.Neurochem. 56: 827–835 (1991).

    Article  PubMed  CAS  Google Scholar 

  20. J. D. Black and J. O. Dolly, Interaction of 125-I labelled botulinum neurotoxins with nerve terminals. I. Ultrastructural autoradiographic localization and quantitation of distinct membrane acceptors for types A and B on motor nerves, J.Cell Biol. 103: 521–534 (1986).

    Article  PubMed  CAS  Google Scholar 

  21. R. S. Williams, C. K. Tse, J. O. Dolly, P. Hambleton, and J. Melling, Radioiodination of botulinum neurotoxin type A with retention of biological activity and its binding to brain synaptosomes, Eur.J.Biochem. 131: 437–445 (1983).

    Article  PubMed  CAS  Google Scholar 

  22. D. M. Evans, R. S. Williams, C. C. Shone, P. Hambleton, J. Melling, and J. O. Dolly, Botulinum neurotoxin type B. Its purification, radioiodination and interaction with rat brain synaptosomal membranes, Eur.J.Biochem. 154: 409–416 (1986).

    Article  PubMed  CAS  Google Scholar 

  23. J. S. Elston, Botulinum toxin A in clinical medicine, J.Physiol.(Paris). 84: 285–289 (1990).

    CAS  Google Scholar 

  24. J. O. Dolly, A. de Paiva, B. Poulain, P. Foran, A. Ashton, and L. Tauc: “Bacterial Protein Toxins, Zbl. BaKt. Suppl. 23,” Witholt et al. ed., Gustav Fischer, Stuttgart, Jena, New York (1992).

    Google Scholar 

  25. G. Schiavo, E. Papini, G. Genna, and C. Montecucco, An intact inter-chain disulphide bond is required for the neurotoxicity of tetanus toxin, Infect.Immun. 58: 41364141 (1990).

    Google Scholar 

  26. B. Poulain, J. D. F. Wadsworth, C. C. Shone, S. Mochida, S. Lande, J. Melling, J. O. Dolly, and L. Tauc, Mutiple domains of Botulinum neurotoxin contribute to its inhibition of transmitter release in Aplysia Neurons, J. Biol. Chem. 264: 21928–21933 (1989).

    PubMed  CAS  Google Scholar 

  27. E. A. Maisey, J. D. F. Wadsworth, B. Poulain, C. C. Shone, J. Melling, P. Gibbs, L. Tauc, and J. O. Dolly, Involvement of the constituent chains of botulinum neurotoxins A and B in the blockade of neurotransmitter release, Eur.J.Biochem. 177: 683–691 (1988).

    Article  PubMed  CAS  Google Scholar 

  28. A. C. Ashton and J. O. Dolly, Characterization of the inhibitory action of botulinum neurotoxin type A on the release of several transmitters from rat cerebrocortical synaptosomes, J.Neurochem. 50: 1808–1816 (1988).

    Article  PubMed  CAS  Google Scholar 

  29. J. D. Black and J. O. Dolly, Selective location of acceptors for botulinum neurotoxin A in the central and peripheral nervous systems, Neuroscience. 23: 767–779 (1987).

    Article  PubMed  CAS  Google Scholar 

  30. B. Poulain, A. de Paiva, J. O. Dolly, U. Weller, and L. Tauc, Differences in the temperature dependencies of uptake of botulinum and tetanus toxins in Aplysia neurons,, Neuroscience Lett. 139: 289–292 (1992).

    Article  CAS  Google Scholar 

  31. M. S. Santos, P. P. Goncalves, and A. P. Carvalho, Release of gamma[3H]aminobutyric acid from synaptosomes: effect of external cations and of ouabain, Brain Res. 547: 135–141 (1991).

    Article  PubMed  CAS  Google Scholar 

  32. J. Molgó, M. Lemeignan, and S. Thesleff, Aminoglycosides and 3,4diaminopyridine on neuromuscular block caused by botulinum type A toxin, Muscle and Nerve. 10: 464–470 (1987).

    Article  PubMed  Google Scholar 

  33. J. L. Halpern, W. H. Habig, H. Trenchard, and J. T. Russel, Effect of tetanus toxin on oxytocin and vasopressin release from nerve endings of the neurohypophysis, J.Neurochem. 55: 2072–2078 (1990).

    Article  PubMed  CAS  Google Scholar 

  34. D. E. Knight, D. A. Tonge, and P. F. Baker, Inhibition of exocytosis in bovine adrenal medullary cells by botulinum toxin type D, Nature. 317: 719–721 (1985).

    Article  PubMed  CAS  Google Scholar 

  35. P. Marxen, F. Bartels, G. Ahnert-Hilger, and H. Bigalke, Distinct targets for tetanus toxin and botulinum A neurotoxins within the signal transducing pathway in chromaffin cells, Naunyn-Schmeideberg’s Arch.Pharmacol. 344: 387–395 (1991).

    Article  CAS  Google Scholar 

  36. M. Verhage, H. McMahon, W. E. J. M. Ghijsen, F. Boomsma, G. Scholter, V. M. Wiegant, and D. G. Nicholls, Differential release of amino acids, neuropeptides, and catecholamines from isolated nerve terminals, Neuron. 6: 517–524 (1991).

    Article  PubMed  CAS  Google Scholar 

  37. M. Matteoli, C. Haimann, F. Torri-Tarelli, J. M. Polak, B. Ceccarelli, and P. De Camilli, Differential effect of a-latrotoxin on exocytosis from small synaptic vesicles and from large dense-core vesicles containing calcitonin gene-related peptide at the frog neuromuscular junction, Proc.Natl.Acad.Sci.USA. 85: 7366–7370 (1988).

    Article  PubMed  CAS  Google Scholar 

  38. A. K. Thureson-Klein, R. L. Klein, P.-C. Zhu, and J.-Y. Kong, Differential release of transmitters and neuropeptides co-stored in central and peripheral neurons, in: “Cellular and Molecular Basis of Synaptic Transmission,” H. Zimmermann ed., Springer-Verlag, Berlin, Heidelberg (1988).

    Google Scholar 

  39. D. V. Pow and D. W. Golding, “Neurosecretion” by aminergic synaptic terminals in vivo - a study of secretory granule exocytosis in the corpus cardiacum of the flying locust, Neuroscience. 22: 1145–1149 (1987).

    Article  PubMed  CAS  Google Scholar 

  40. J. Cuadras, Non-synaptic release from dense-cored vesicles occurs at all terminal types in crayfish neuropile, Brain Res. 477: 332–335 (1989).

    Article  PubMed  CAS  Google Scholar 

  41. R. Robitaille, E. M. Adler, and M. P. Charlton, Strategic location of calcium channels at transmitter release sites of frog neuromuscular synapses, Neuron. 5: 773–779 (1990).

    Article  PubMed  CAS  Google Scholar 

  42. H. T. McMahon and D. G. Nicholls, The bioenergetics of neurotransmitter release, Biochim.Biophys.Acta. 1059: 243–364 (1991).

    Article  PubMed  CAS  Google Scholar 

  43. P. K. Janicki and E. Habermann, Tetanus and botulinum toxins inhibit, and black widow spider venom stimulates the release of methionine-enkephalin-like material in vitro, J.Neurochem. 41: 395–402 (1983).

    Article  PubMed  CAS  Google Scholar 

  44. H. T. McMahon, P. Foran, J. O. Dolly, M. Verhage, V. M. Wiegant, and D. G. Nicholls, Tetanus and botulinum toxins type A and B inhibit glutamate, GABA, aspartate and met-enkephalin release from synaptosomes: clues to the locus of action, J.Biol.Chem. In Press (1992).

    Google Scholar 

  45. F. Vyskocil, E. Nikolsky, and C. Edwards, An analysis of the mechanisms underlying the non-quantal release of acetylcholine at the neuromuscular junction, Neuroscience. 9: 429–435 (1983).

    Article  PubMed  CAS  Google Scholar 

  46. C. B. Gundersen and D. J. Jenden, Spontaneous output of acetylcholine from rat diaphragm preparations declines after treatment with botulinum toxin, J.Pharmacol.Exp.Ther. 224: 265–268 (1983).

    PubMed  CAS  Google Scholar 

  47. F. Vyskocil, Inhibition of non-quantal leakage by 2(4phenylpiperidine)cyclohexanol in the mouse diaphragm, Neuroscience Lett. 59: 277–280 (1985).

    Article  CAS  Google Scholar 

  48. S. D. Merriney, S. H. Young, and A. D. Grinell, Constraints on the interpretation of nonquantal acetylcholine release from frog neuromuscular junctions, Proc.Natl.Acad.Sci. USA. 86: 2098–2102 (1989).

    Article  Google Scholar 

  49. B. Ceccarelli, R. Fesce, F. Grohavaz, and C. Haimann, The effect of potassium on exocytosis of transmitter at the frog neuromuscular junction, J.Physiol.(Lond.). 401: 163183 (1988).

    Google Scholar 

  50. E. S. Vizi, K. Gyires, G. T. Somogyi, and G. Ungvary, Evidence that transmitter can be released from regions of the nerve cell other than presynaptic axon terminal: axonal release of acetylcholine without modulation, Neuroscience. 10: 967–972 (1983).

    Article  PubMed  CAS  Google Scholar 

  51. M. L. Vitale, A. Rodriguez del Castillo, L. Tchakarov, and J.-M. Trifaro, Cortical filamentous actin disassembly and scinderin redistribution during chromaffin cell stimulation precede exocytosis, a phenomenon not exhibited by gelsolin, J.Cell Biol. 113: 1057–1067 (1991).

    Article  PubMed  CAS  Google Scholar 

  52. R. H. Chow, L. von Rüden, and E. Neher, Delay in vesicle fusion revealed by electrochemical monitoring of single secretory events in adrenal chromaffin cells, Nature. 356: 60–63 (1992).

    Article  PubMed  CAS  Google Scholar 

  53. S. Terakawa, J.-H. Fan, K. Kumakuru, and M. Ohara-Imaizumi, Quantitative analysis of exocytosis directly visualized in living chromaffin cells, Neuroscience Lett. 123: 82–86 (1991).

    Article  CAS  Google Scholar 

  54. P. Marxen and H. Bigalke, Tetanus toxin and botulinum A toxins inhibit stimulated F-actin rearrangements in chromaffin cells, Neuroreport. 2: 33–36 (1991).

    Article  PubMed  CAS  Google Scholar 

  55. H. von Grafenstein, R. Borges, and D. E. Knight, The effect of botulinum toxin type D on the triggered and constitutive exocytosis/endocytosis cycles in cultures of bovine adrenal medullary cells, FEBS Lett. 298: 118–122 (1992).

    Article  Google Scholar 

  56. E. G. Gray, Presynaptic microtubules and their association with synaptic vesicles, Proc.Roy.Soc.Lond.(Biol.]. 190: 369–372 (1975).

    Article  Google Scholar 

  57. N. Hirokawa, K. Sobue, K. Kanda, A. Maruda, and H. Yorifugi, The cytoskeletal architecture of the presynaptic terminal and molecular structure of synapsin I, J.Cell Biol. 108: 111–126 (1989).

    Article  PubMed  CAS  Google Scholar 

  58. P. R. Gordon-Weeks, R. D. Burgoyne, and E. G. Gray, Presynaptic microtubules: organization and assembly/ disassembly, Neurosciece. 7: 739–749 (1982).

    Article  CAS  Google Scholar 

  59. R. D. Burgoyne and R. Cumming, Taxol stabilizes synaptosomal microtubules without inhibiting acetylcholine release, Brain Res. 280: 190–193 (1983).

    Article  PubMed  CAS  Google Scholar 

  60. L. L. Simpson, The origin, structure, and pharmacological activity of botulinum toxin, Pharmacol.Rev. 33: 155–188 (1981).

    PubMed  CAS  Google Scholar 

  61. J. D. Black and J. O. Dolly, Interaction of 125 I-labeled botulinum neurotoxins with nerve terminals. II. Autoradiographic evidence for its uptake into motor nerves by acceptor-mediated endocytosis, J.Cell Biol. 103: 535–544 (1986).

    Article  PubMed  CAS  Google Scholar 

  62. R. G. Parton, C. D. Ockleford, and D. R. Critchley, Tetanus toxin binding to mouse spinal cord cells: an evaluation of the role of gangliosides in toxin internalization, Brain Res. 475: 118–127 (1988).

    Article  PubMed  CAS  Google Scholar 

  63. R. G. Parton, C. D. Ockleford, and D. R. Critchley, A study of the mechanism of internalization of tetanus toxin by primary mouse spinal cord cultures, J.Neurochem. 49: 1057–1068 (1987).

    Article  PubMed  CAS  Google Scholar 

  64. K. A. Manning, J. T. Erichsen, and C. Evinger, Retrograde transneuronal transport properties of fragment C of tetanus toxin, Neuroscience. 34: 251–263 (1990).

    Article  PubMed  CAS  Google Scholar 

  65. G. R. Tibbs, A. P. Barrie, F. J. E. Van Mieghem, H. T. McMahon, and D. G. Nicholls, Repetitive action potentials in isolated nerve terminals in the presence of 4aminopyridine: effects on cytosolic free Cat+ and glutamate release, J.Neurochem. 53: 1693–1699 (1989).

    Article  PubMed  CAS  Google Scholar 

  66. A. Banerjee and R. F. Luduena, Kinetics of association and dissociation of colchicine-tubulin complex from brain and renal tubulin. Evidence for the existence of multiple isotypes of tubulin in brain with differential affinity to colchicine, FEBS Lett. 219: 103–107 (1987).

    Google Scholar 

  67. A. Banerjee and R. F. Luduena, Distinct colchicine binding kinetics of bovine brain tubulin lacking the type III isotype of beta-tubulin, J.Biol.Chem. 266: 1689–1691 (1991).

    PubMed  CAS  Google Scholar 

  68. P. W. Baas and M. M. Black, Individual microtubules in the axon consist of domains that differ in both composition and stability, J.Cell Biol. 111: 495–509 (1991).

    Article  Google Scholar 

  69. P. W. Baas, T. Slaughter, A. Brown, and M. M. Black, Microtubule dynamics in axons and dendrites, J.Neurosci.Res. 30: 134–153 (1991).

    Article  PubMed  CAS  Google Scholar 

  70. R. H. Miller, R. J. Lasek, and M. J. Katz, Preferred microtubules for vesicle transport in lobster axons, Science. 235: 220–222 (1987).

    Article  PubMed  CAS  Google Scholar 

  71. H. Koike, M. Matsumoto, and Y. Umitso, Selective axonal transport in a single cholinergic axon of Aplysia-role for colchicine-resistant microtubules, Neuroscience. 32: 539–555 (1989).

    Article  PubMed  CAS  Google Scholar 

  72. F. F. Severin, N. A. Shanina, S. A. Kuznetsov, and V. I. Gelfand, MAP2mediated binding of chromaffin granules to microtubules, FEBS Lett. 282: 65–68 (1991).

    Article  PubMed  CAS  Google Scholar 

  73. Z. Luo, B. Shafit-Zagardo, and J. Erlichman, Identification of the MAP2- and P75-binding domain in the regulatory subunit (RII beta) of type II cAMP-dependent protein kinase, J.Biol.Chem. 265: 21804–21810 (1990).

    PubMed  CAS  Google Scholar 

  74. R. Donato, I. Giambanco, and M. C. Aisa, Molecular interaction of S-100 proteins with microtubule proteins in vitro, J.Neurochem. 53: 566–571 (1989).

    Article  PubMed  CAS  Google Scholar 

  75. Shimada, H. Ishikawa, and K. Wakabayashi, Role of microtubules in hormone secretion function of the rat anterior pituitary, Protoplasma. Supp1. 2: 145–157 (1988).

    Google Scholar 

  76. K. Parczyk, W. Haase, and C. Kondor-Koch, Microtubules are involved in the secretion of proteins at the apical cell surface of the polarized epithelial cell Madrin-Darby canine kidney, J.Biol.Chem. 264: 16837–16846 (1989).

    PubMed  CAS  Google Scholar 

  77. G. Herman, G. Busson, M. J. Gorbunoff, P. Mauduit, S. N. Timasheff, and B. Rossignol, Colchicine analogues that bind reversibility to tubulin define microtubular requirements for newly synthesized protein secretion in rat lacrimal gland, Proc.Natl.Acad. Sci. USA. 86: 4515–4519 (1989).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer Science+Business Media New York

About this chapter

Cite this chapter

Ashton, A.C., de Paiva, A.M., Poulain, B., Tauc, L., Dolly, J.O. (1993). Factors Underlying the Characteristic Inhibition of the Neuronal Release of Transmitters by Tetanus and Various Botulinum Toxins. In: DasGupta, B.R. (eds) Botulinum and Tetanus Neurotoxins. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9542-4_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-9542-4_20

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9544-8

  • Online ISBN: 978-1-4757-9542-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics