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 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 gamma and epsilon subunit. We also examined AChR distribution at the endplate by immunofluorescence assays. No differences between wt and mdx fibers were found in the gamma/epsilon 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 gamma/epsilon 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.

Automated summary

This study found that the absence of dystrophin does not affect the distribution of AChRs at the endplate, but the formation and disassembly of extra-synaptic AChR clusters may be regulated differently in mdx mice.