Structure and function of the neuromuscular junction in young adultmdx mice

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Abstract
Dystrophin, the protein product of the gene responsible for X-linked muscular dystrophies, shares structural features with the cytoskeletal proteins spectrin and α-actinin. Like spectrin, it is localized at the cytoplasmic surface of the sarcolemma and is particularly concentrated in the subsynaptic region of the neuromuscular junction.Mdx mice have a profound deficiency of dystrophin and develop a necrotizing myopathy in the first weeks of life. Abnormalities of the neuromuscular junction, including a redistribution of postsynaptic molecules and reduction in synaptic folding, are also observed. We have studied these mice to see whether the lack of dystrophin has a specific effect on the structure and function of their neuromuscular junctions. Using a fore-limb muscle from 8 week oldmdx mice we confirm the previously described postsynaptic structural changes and in addition show that many nerve terminals are abnormally complex. We demonstrate that these structural abnormalities are found exclusively at neuromuscular junctions on regenerated muscle fibres. Despite these structural abnormalities, miniature endplate potential frequency, the quantal content of endplate potentials, the amplitude and time course of miniature endplate currents and the number of acetylcholine receptors at the postsynaptic membrane are normal inmdx mice of this age. We conclude that in themdx mouse the absence of dystrophin from the postsynaptic membrane has little direct effect on the function of the neuromuscular junction but that degeneration and regeneration of muscle fibres leads to remodelling of both its pre- and postsynaptic components.