Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Body Patterning / physiology*
  • CD24 Antigen / genetics
  • Calcium / metabolism
  • Calcium Channels, L-Type / deficiency
  • Calcium Channels, L-Type / physiology*
  • Cell Line, Transformed
  • Electron Microscope Tomography / methods
  • Embryo, Mammalian
  • Excitatory Postsynaptic Potentials / genetics
  • Homeodomain Proteins
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / embryology*
  • Neuromuscular Junction / embryology*
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / physiology*
  • Neuromuscular Junction / ultrastructure
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Nicotinic / metabolism
  • Transcription Factors / deficiency
  • Up-Regulation / genetics


  • CD24 Antigen
  • Cacnb1 protein, mouse
  • Calcium Channels, L-Type
  • Cd24a protein, mouse
  • Homeodomain Proteins
  • Receptors, Nicotinic
  • Transcription Factors
  • Hb9 protein, mouse
  • MuSK protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • Calcium