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Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in mdx Mouse
Dystrophin is a cytoskeletal protein contributing to the organization of the neuromuscular junction. In Duchenne muscular dystrophy, due to dystrophin absence, the distribution of endplate acetylcholine receptors (AChRs) becomes disorganized. It is still debated whether this is due to the absence of...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696329/ https://www.ncbi.nlm.nih.gov/pubmed/36430996 http://dx.doi.org/10.3390/life12111861 |
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author | Morotti, Marta Gaeta, Alessandro Limatola, Cristina Catalano, Myriam Di Castro, Maria Amalia Grassi, Francesca |
author_facet | Morotti, Marta Gaeta, Alessandro Limatola, Cristina Catalano, Myriam Di Castro, Maria Amalia Grassi, Francesca |
author_sort | Morotti, Marta |
collection | PubMed |
description | Dystrophin is a cytoskeletal protein contributing to the organization of the neuromuscular junction. In Duchenne muscular dystrophy, due to dystrophin absence, the distribution of endplate acetylcholine receptors (AChRs) becomes disorganized. It is still debated whether this is due to the absence of dystrophin or to the repeated damage/regeneration cycles typical of dystrophic muscle. We addressed this controversy studying the endplate in the first 3 postnatal weeks, when muscle damage in dystrophic (mdx) mice is minimal. By synaptic and extra-synaptic patch-clamp recordings in acutely dissociated mdx and wt muscle fibers, we recorded unitary events due to openings of AChR-channels containing the γ and ε subunit. We also examined AChR distribution at the endplate by immunofluorescence assays. No differences between wt and mdx fibers were found in the γ/ε switch, nor in the AChR organization at the endplates up to 21 postnatal days. Conversely, we detected a delayed appearance and disappearance of patches with high channel opening frequency in mdx fibers. Our data emphasize that the innervation-dependent γ/ε switch and AChR organization in the endplate are not affected by the absence of dystrophin, while extra-synaptic AChR cluster formation and disassembly could be differentially regulated in mdx mice. |
format | Online Article Text |
id | pubmed-9696329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96963292022-11-26 Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in mdx Mouse Morotti, Marta Gaeta, Alessandro Limatola, Cristina Catalano, Myriam Di Castro, Maria Amalia Grassi, Francesca Life (Basel) Article Dystrophin is a cytoskeletal protein contributing to the organization of the neuromuscular junction. In Duchenne muscular dystrophy, due to dystrophin absence, the distribution of endplate acetylcholine receptors (AChRs) becomes disorganized. It is still debated whether this is due to the absence of dystrophin or to the repeated damage/regeneration cycles typical of dystrophic muscle. We addressed this controversy studying the endplate in the first 3 postnatal weeks, when muscle damage in dystrophic (mdx) mice is minimal. By synaptic and extra-synaptic patch-clamp recordings in acutely dissociated mdx and wt muscle fibers, we recorded unitary events due to openings of AChR-channels containing the γ and ε subunit. We also examined AChR distribution at the endplate by immunofluorescence assays. No differences between wt and mdx fibers were found in the γ/ε switch, nor in the AChR organization at the endplates up to 21 postnatal days. Conversely, we detected a delayed appearance and disappearance of patches with high channel opening frequency in mdx fibers. Our data emphasize that the innervation-dependent γ/ε switch and AChR organization in the endplate are not affected by the absence of dystrophin, while extra-synaptic AChR cluster formation and disassembly could be differentially regulated in mdx mice. MDPI 2022-11-12 /pmc/articles/PMC9696329/ /pubmed/36430996 http://dx.doi.org/10.3390/life12111861 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Morotti, Marta Gaeta, Alessandro Limatola, Cristina Catalano, Myriam Di Castro, Maria Amalia Grassi, Francesca Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in mdx Mouse |
title | Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in mdx Mouse |
title_full | Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in mdx Mouse |
title_fullStr | Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in mdx Mouse |
title_full_unstemmed | Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in mdx Mouse |
title_short | Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in mdx Mouse |
title_sort | early developmental changes of muscle acetylcholine receptors are little influenced by dystrophin absence in mdx mouse |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696329/ https://www.ncbi.nlm.nih.gov/pubmed/36430996 http://dx.doi.org/10.3390/life12111861 |
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