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eNeuro. 2017 Aug 10;4(4). pii: ENEURO.0051-17.2017. doi: 10.1523/ENEURO.0051-17.2017. eCollection 2017 Jul-Aug.

Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse.

Author information

1
Laboratory of Cellular and Molecular Neurobiology, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Campus of Bellvitge, University of Barcelona, Hospitalet de Llobregat, Barcelona 08907, Spain.
2
Institut d'Investigació Biomèdica de Bellvitge - Biomedical Research Institute of Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona 08907, Spain.
3
Institute of Neurosciences, University of Barcelona, Barcelona 08035, Spain.
4
School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom.
5
Department of Neurology, University of Washington, Seattle, WA 98195.

Abstract

ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood-brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS).

KEYWORDS:

ATP release; action potential; clostridial toxin; electrophysiology; myelin; optic nerve

PMID:
28798954
PMCID:
PMC5550839
DOI:
10.1523/ENEURO.0051-17.2017
[Indexed for MEDLINE]
Free PMC Article

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