L-type calcium channels mediate acetylcholine receptor aggregation on cultured muscle

Rebecca B R Milholland, Christopher Dulla, Herman Gordon

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Agrin activation of muscle specific kinase (MuSK) initiates postsynaptic development on skeletal muscle that includes the aggregation of acetylcholine receptors (AChRs; Glass et al. [1996]: Cell 85: 513-523; Gautam et al. [1996]: Cell 85: 525-535). Although the agrin/MuSK signaling pathway remains largely unknown, changes in intracellular calcium levels are required for agrin-induced AChR aggregation (Megeath and Fallon [1998]: J Neurosci 18: 672-678). Here, we show that L-type calcium channels (L-CaChs) are required for full agrin-induced aggregation of AChRs and sufficient to induce agrin-independent AChR aggregation. Blockade of L-CaChs in muscle cultures inhibited agrin-induced AChR aggregation but not tyrosine phosphorylation of MuSK or AChR β subunits. Activation of L-CaChs in the absence of agrin induced AChR aggregation but not tyrosine phosphorylation of MuSK or AChR β subunits. Agrin responsiveness was significantly reduced in primary muscle cultures from the muscular dysgenesis mouse, a natural mutant, which does not express the L-CaCh. Our results establish a novel role for L-CaChs as important sources of the intracellular calcium necessary for the aggregation of AChRs.

Original languageEnglish (US)
Pages (from-to)987-998
Number of pages12
JournalDevelopmental Neurobiology
Volume67
Issue number8
DOIs
StatePublished - Jul 2007

Fingerprint

Agrin
Receptor Aggregation
L-Type Calcium Channels
Cholinergic Receptors
Muscles
Phosphotransferases
Tyrosine
Phosphorylation
Calcium
Skeletal Muscle

Keywords

  • Acetylcholine receptor
  • Aggregation
  • Agrin
  • Calcium
  • Cluster
  • Dysgenic mouse
  • Intracellular signaling
  • L-type calcium channel
  • Muscle specific kinase
  • MuSK
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

L-type calcium channels mediate acetylcholine receptor aggregation on cultured muscle. / Milholland, Rebecca B R; Dulla, Christopher; Gordon, Herman.

In: Developmental Neurobiology, Vol. 67, No. 8, 07.2007, p. 987-998.

Research output: Contribution to journalArticle

Milholland, Rebecca B R ; Dulla, Christopher ; Gordon, Herman. / L-type calcium channels mediate acetylcholine receptor aggregation on cultured muscle. In: Developmental Neurobiology. 2007 ; Vol. 67, No. 8. pp. 987-998.
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