How myasthenia gravis alters the safety factor for neuromuscular transmission

Robert L. Ruff, Vanda A. Lennon

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Myasthenia gravis (MG), the most common of autoimmune myasthenic syndromes, is characterized by antibodies directed against the skeletal muscle acetylcholine receptors (AChRs). Endplate Na+ channels ensure the efficiency of neuromuscular transmission by reducing the threshold depolarization needed to trigger an action potential. Postsynaptic AChRs and voltage-gated Na+ channels are both lost from the neuromuscular junction in MG. This study examined the impact of postsynaptic voltage-gated Na+ channel loss on the safety factor for neuromuscular transmission. In intercostal nerve-muscle preparations from MG patients, we found that endplate AChR loss decreases the size of the endplate potential, and endplate Na+ channel loss increases the threshold depolarization needed to produce a muscle action potential. To evaluate whether AChR-specific antibody impairs the function of Na+ channels, we tested omohyoid nerve-muscle preparations from rats injected with monoclonal myasthenogenic IgG (passive transfer model of MG [PTMG]). The AChR antibody that produces PTMG did not alter the function of Na+ channels. We conclude that loss of endplate Na+ channels in MG is due to complement-mediated loss of endplate membrane rather than a direct effect of myasthenogenic antibodies on endplate Na+ channels.

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalJournal of neuroimmunology
Volume201-202
Issue numberC
DOIs
StatePublished - Sep 15 2008

Keywords

  • Acetylcholine receptor
  • Action potential threshold
  • Myasthenia gravis
  • Passively transferred MG
  • Safety factor
  • Sodium channels

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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