Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors

Fujun Chen, Yun Liu, Yoshie Sugiura, Paul D. Allen, Ronald G. Gregg, Weichun Lin

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 Ca2+ 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 Ca2+ influx through the L-type Ca2+ channel. Our findings indicate that the skeletal muscle DHPR retrogradely regulates the patterning and formation of the NMJ.

Original languageEnglish (US)
Pages (from-to)570-578
Number of pages9
JournalNature Neuroscience
Volume14
Issue number5
DOIs
StatePublished - May 2011
Externally publishedYes

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L-Type Calcium Channels
Skeletal Muscle
Neuromuscular Junction
Muscles
Excitation Contraction Coupling
Intrinsic Factor
Vertebrates

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors. / Chen, Fujun; Liu, Yun; Sugiura, Yoshie; Allen, Paul D.; Gregg, Ronald G.; Lin, Weichun.

In: Nature Neuroscience, Vol. 14, No. 5, 05.2011, p. 570-578.

Research output: Contribution to journalArticle

Chen, F, Liu, Y, Sugiura, Y, Allen, PD, Gregg, RG & Lin, W 2011, 'Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors', Nature Neuroscience, vol. 14, no. 5, pp. 570-578. https://doi.org/10.1038/nn.2792
Chen, Fujun ; Liu, Yun ; Sugiura, Yoshie ; Allen, Paul D. ; Gregg, Ronald G. ; Lin, Weichun. / Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors. In: Nature Neuroscience. 2011 ; Vol. 14, No. 5. pp. 570-578.
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