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The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction

BACKGROUND: Various protein kinase C (PKC) isoforms contribute to the phosphorylating activity that modulates neurotransmitter release. In previous studies we showed that nPKCε is confined in the presynaptic site of the neuromuscular junction and its presynaptic function is activity-dependent. Furth...

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Autores principales: Obis, Teresa, Hurtado, Erica, Nadal, Laura, Tomàs, Marta, Priego, Mercedes, Simon, Anna, Garcia, Neus, Santafe, Manel M., Lanuza, Maria A., Tomàs, Josep
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665914/
https://www.ncbi.nlm.nih.gov/pubmed/26625935
http://dx.doi.org/10.1186/s13041-015-0171-5
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author Obis, Teresa
Hurtado, Erica
Nadal, Laura
Tomàs, Marta
Priego, Mercedes
Simon, Anna
Garcia, Neus
Santafe, Manel M.
Lanuza, Maria A.
Tomàs, Josep
author_facet Obis, Teresa
Hurtado, Erica
Nadal, Laura
Tomàs, Marta
Priego, Mercedes
Simon, Anna
Garcia, Neus
Santafe, Manel M.
Lanuza, Maria A.
Tomàs, Josep
author_sort Obis, Teresa
collection PubMed
description BACKGROUND: Various protein kinase C (PKC) isoforms contribute to the phosphorylating activity that modulates neurotransmitter release. In previous studies we showed that nPKCε is confined in the presynaptic site of the neuromuscular junction and its presynaptic function is activity-dependent. Furthermore, nPKCε regulates phorbol ester-induced acetylcholine release potentiation, which further indicates that nPKCε is involved in neurotransmission. The present study is designed to examine the nPKCε involvement in transmitter release at the neuromuscular junction. RESULTS: We use the specific nPKCε translocation inhibitor peptide εV1-2 and electrophysiological experiments to investigate the involvement of this isoform in acetylcholine release. We observed that nPKCε membrane translocation is key to the synaptic potentiation of NMJ, being involved in several conditions that upregulate PKC isoforms coupling to acetylcholine (ACh) release (incubation with high Ca(2+), stimulation with phorbol esters and protein kinase A, stimulation with adenosine 3′,5′-cyclic monophosphorothioate, 8-Bromo-, Rp-isomer, sodium salt -Sp-8-BrcAMP-). In all these conditions, preincubation with the nPKCε translocation inhibitor peptide (εV1-2) impairs PKC coupling to acetylcholine release potentiation. In addition, the inhibition of nPKCε translocation and therefore its activity impedes that presynaptic muscarinic autoreceptors and adenosine autoreceptors modulate transmitter secretion. CONCLUSIONS: Together, these results point to the importance of nPKCε isoform in the control of acetylcholine release in the neuromuscular junction.
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spelling pubmed-46659142015-12-02 The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction Obis, Teresa Hurtado, Erica Nadal, Laura Tomàs, Marta Priego, Mercedes Simon, Anna Garcia, Neus Santafe, Manel M. Lanuza, Maria A. Tomàs, Josep Mol Brain Research BACKGROUND: Various protein kinase C (PKC) isoforms contribute to the phosphorylating activity that modulates neurotransmitter release. In previous studies we showed that nPKCε is confined in the presynaptic site of the neuromuscular junction and its presynaptic function is activity-dependent. Furthermore, nPKCε regulates phorbol ester-induced acetylcholine release potentiation, which further indicates that nPKCε is involved in neurotransmission. The present study is designed to examine the nPKCε involvement in transmitter release at the neuromuscular junction. RESULTS: We use the specific nPKCε translocation inhibitor peptide εV1-2 and electrophysiological experiments to investigate the involvement of this isoform in acetylcholine release. We observed that nPKCε membrane translocation is key to the synaptic potentiation of NMJ, being involved in several conditions that upregulate PKC isoforms coupling to acetylcholine (ACh) release (incubation with high Ca(2+), stimulation with phorbol esters and protein kinase A, stimulation with adenosine 3′,5′-cyclic monophosphorothioate, 8-Bromo-, Rp-isomer, sodium salt -Sp-8-BrcAMP-). In all these conditions, preincubation with the nPKCε translocation inhibitor peptide (εV1-2) impairs PKC coupling to acetylcholine release potentiation. In addition, the inhibition of nPKCε translocation and therefore its activity impedes that presynaptic muscarinic autoreceptors and adenosine autoreceptors modulate transmitter secretion. CONCLUSIONS: Together, these results point to the importance of nPKCε isoform in the control of acetylcholine release in the neuromuscular junction. BioMed Central 2015-12-01 /pmc/articles/PMC4665914/ /pubmed/26625935 http://dx.doi.org/10.1186/s13041-015-0171-5 Text en © Obis et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Obis, Teresa
Hurtado, Erica
Nadal, Laura
Tomàs, Marta
Priego, Mercedes
Simon, Anna
Garcia, Neus
Santafe, Manel M.
Lanuza, Maria A.
Tomàs, Josep
The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction
title The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction
title_full The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction
title_fullStr The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction
title_full_unstemmed The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction
title_short The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction
title_sort novel protein kinase c epsilon isoform modulates acetylcholine release in the rat neuromuscular junction
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665914/
https://www.ncbi.nlm.nih.gov/pubmed/26625935
http://dx.doi.org/10.1186/s13041-015-0171-5
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