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

41 Scopus citations

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

ASJC Scopus subject areas

  • Neuroscience(all)

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