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Nat Neurosci. 2011 May;14(5):570-7. doi: 10.1038/nn.2792. Epub 2011 Mar 27.

Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors.

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1
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Abstract

Developing skeletal myofibers in vertebrates are intrinsically 'pre-patterned' for motor nerve innervation. However, the intrinsic factors that regulate muscle pre-patterning remain unknown. We found that a functional skeletal muscle dihydropyridine receptor (DHPR, the L-type Ca(2+) channel in muscle) was required for muscle pre-patterning during the development of the neuromuscular junction (NMJ). Targeted deletion of the β1 subunit of DHPR (Cacnb1) in mice led to muscle pre-patterning defects, aberrant innervation and precocious maturation of the NMJ. Reintroducing Cacnb1 into Cacnb1(-/-) muscles reversed the pre-patterning defects and restored normal development of the NMJ. The mechanism by which DHPRs govern muscle pre-patterning is independent of their role in excitation-contraction coupling, but requires Ca(2+) influx through the L-type Ca(2+) channel. Our findings indicate that the skeletal muscle DHPR retrogradely regulates the patterning and formation of the NMJ.

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PMID:
21441923
PMCID:
PMC3083454
DOI:
10.1038/nn.2792
[Indexed for MEDLINE]
Free PMC Article
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