Cargando…

Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes

Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, causes serious neurological disorders in animals. ETX can bind to the white matter of the brain and the oligodendrocytes, which are the cells forming the myelin sheath around neuron axons in the white matter of the central nervo...

Descripción completa

Detalles Bibliográficos
Autores principales: Bossu, Jean Louis, Wioland, Laetitia, Doussau, Frédéric, Isope, Philippe, Popoff, Michel R., Poulain, Bernard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020416/
https://www.ncbi.nlm.nih.gov/pubmed/31935961
http://dx.doi.org/10.3390/toxins12010036
_version_ 1783497739940659200
author Bossu, Jean Louis
Wioland, Laetitia
Doussau, Frédéric
Isope, Philippe
Popoff, Michel R.
Poulain, Bernard
author_facet Bossu, Jean Louis
Wioland, Laetitia
Doussau, Frédéric
Isope, Philippe
Popoff, Michel R.
Poulain, Bernard
author_sort Bossu, Jean Louis
collection PubMed
description Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, causes serious neurological disorders in animals. ETX can bind to the white matter of the brain and the oligodendrocytes, which are the cells forming the myelin sheath around neuron axons in the white matter of the central nervous system. After binding to oligodendrocytes, ETX causes demyelination in rat cerebellar slices. We further investigated the effects of ETX on cerebellar oligodendrocytes and found that ETX induced small transmembrane depolarization (by ~ +6.4 mV) in rat oligodendrocytes primary cultures. This was due to partial inhibition of the transmembrane inward rectifier potassium current (Kir). Of the two distinct types of Kir channel conductances (~25 pS and ~8.5 pS) recorded in rat oligodendrocytes, we found that ETX inhibited the large-conductance one. This inhibition did not require direct binding of ETX to a Kir channel. Most likely, the binding of ETX to its membrane receptor activates intracellular pathways that block the large conductance Kir channel activity in oligodendrocyte. Altogether, these findings and previous observations pinpoint oligodendrocytes as a major target for ETX. This supports the proposal that ETX might be a cause for Multiple Sclerosis, a disease characterized by myelin damage.
format Online
Article
Text
id pubmed-7020416
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70204162020-03-09 Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes Bossu, Jean Louis Wioland, Laetitia Doussau, Frédéric Isope, Philippe Popoff, Michel R. Poulain, Bernard Toxins (Basel) Article Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, causes serious neurological disorders in animals. ETX can bind to the white matter of the brain and the oligodendrocytes, which are the cells forming the myelin sheath around neuron axons in the white matter of the central nervous system. After binding to oligodendrocytes, ETX causes demyelination in rat cerebellar slices. We further investigated the effects of ETX on cerebellar oligodendrocytes and found that ETX induced small transmembrane depolarization (by ~ +6.4 mV) in rat oligodendrocytes primary cultures. This was due to partial inhibition of the transmembrane inward rectifier potassium current (Kir). Of the two distinct types of Kir channel conductances (~25 pS and ~8.5 pS) recorded in rat oligodendrocytes, we found that ETX inhibited the large-conductance one. This inhibition did not require direct binding of ETX to a Kir channel. Most likely, the binding of ETX to its membrane receptor activates intracellular pathways that block the large conductance Kir channel activity in oligodendrocyte. Altogether, these findings and previous observations pinpoint oligodendrocytes as a major target for ETX. This supports the proposal that ETX might be a cause for Multiple Sclerosis, a disease characterized by myelin damage. MDPI 2020-01-06 /pmc/articles/PMC7020416/ /pubmed/31935961 http://dx.doi.org/10.3390/toxins12010036 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bossu, Jean Louis
Wioland, Laetitia
Doussau, Frédéric
Isope, Philippe
Popoff, Michel R.
Poulain, Bernard
Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes
title Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes
title_full Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes
title_fullStr Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes
title_full_unstemmed Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes
title_short Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes
title_sort epsilon toxin from clostridium perfringens causes inhibition of potassium inward rectifier (kir) channels in oligodendrocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020416/
https://www.ncbi.nlm.nih.gov/pubmed/31935961
http://dx.doi.org/10.3390/toxins12010036
work_keys_str_mv AT bossujeanlouis epsilontoxinfromclostridiumperfringenscausesinhibitionofpotassiuminwardrectifierkirchannelsinoligodendrocytes
AT wiolandlaetitia epsilontoxinfromclostridiumperfringenscausesinhibitionofpotassiuminwardrectifierkirchannelsinoligodendrocytes
AT doussaufrederic epsilontoxinfromclostridiumperfringenscausesinhibitionofpotassiuminwardrectifierkirchannelsinoligodendrocytes
AT isopephilippe epsilontoxinfromclostridiumperfringenscausesinhibitionofpotassiuminwardrectifierkirchannelsinoligodendrocytes
AT popoffmichelr epsilontoxinfromclostridiumperfringenscausesinhibitionofpotassiuminwardrectifierkirchannelsinoligodendrocytes
AT poulainbernard epsilontoxinfromclostridiumperfringenscausesinhibitionofpotassiuminwardrectifierkirchannelsinoligodendrocytes