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

  • Anthony C. Ashton
  • Anton M. de Paiva
  • Bernard Poulain
  • Ladislav Tauc
  • J. Oliver Dolly

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.

Keywords

Botulinum Toxin Chromaffin Cell Transmitter Release Botulinum Neurotoxin Tetanus Toxin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Anthony C. Ashton
    • 1
  • Anton M. de Paiva
    • 1
  • Bernard Poulain
    • 2
  • Ladislav Tauc
    • 2
  • J. Oliver Dolly
    • 1
  1. 1.Department of Biochemistry, Imperial College of ScienceTechnology and MedicineLondonUK
  2. 2.Laboratoire de Neurobiologie Cellulaire et MoléculaireCNRSGif-sur-Yvette CedexFrance

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