Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in <i>mdx</i> 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...
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MDPI AG
2022-11-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/11/1861 |
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| author | Marta Morotti Alessandro Gaeta Cristina Limatola Myriam Catalano Maria Amalia Di Castro Francesca Grassi |
| author_facet | Marta Morotti Alessandro Gaeta Cristina Limatola Myriam Catalano Maria Amalia Di Castro Francesca Grassi |
| author_sort | Marta Morotti |
| collection | DOAJ |
| 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 (<i>mdx</i>) mice is minimal. By synaptic and extra-synaptic patch-clamp recordings in acutely dissociated <i>mdx</i> 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 <i>mdx</i> 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 <i>mdx</i> 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 <i>mdx</i> mice. |
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| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T18:12:39Z |
| publishDate | 2022-11-01 |
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| series | Life |
| spelling | doaj.art-400a3e4f3eab445790e30de31e272a572023-11-24T08:57:07ZengMDPI AGLife2075-17292022-11-011211186110.3390/life12111861Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in <i>mdx</i> MouseMarta Morotti0Alessandro Gaeta1Cristina Limatola2Myriam Catalano3Maria Amalia Di Castro4Francesca Grassi5Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia, Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, ItalyDystrophin 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 (<i>mdx</i>) mice is minimal. By synaptic and extra-synaptic patch-clamp recordings in acutely dissociated <i>mdx</i> 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 <i>mdx</i> 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 <i>mdx</i> 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 <i>mdx</i> mice.https://www.mdpi.com/2075-1729/12/11/1861Duchenne muscular dystrophyneuromuscular junctionacetylcholine receptorsdystrophic muscle<i>mdx</i>receptor clustering |
| spellingShingle | Marta Morotti Alessandro Gaeta Cristina Limatola Myriam Catalano Maria Amalia Di Castro Francesca Grassi Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in <i>mdx</i> Mouse Life Duchenne muscular dystrophy neuromuscular junction acetylcholine receptors dystrophic muscle <i>mdx</i> receptor clustering |
| title | Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in <i>mdx</i> Mouse |
| title_full | Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in <i>mdx</i> Mouse |
| title_fullStr | Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in <i>mdx</i> Mouse |
| title_full_unstemmed | Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in <i>mdx</i> Mouse |
| title_short | Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in <i>mdx</i> Mouse |
| title_sort | early developmental changes of muscle acetylcholine receptors are little influenced by dystrophin absence in i mdx i mouse |
| topic | Duchenne muscular dystrophy neuromuscular junction acetylcholine receptors dystrophic muscle <i>mdx</i> receptor clustering |
| url | https://www.mdpi.com/2075-1729/12/11/1861 |
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