How myasthenia gravis alters the safety factor for neuromuscular transmission

Robert L. Ruff, Vanda A. Lennon

Research output: Contribution to journalArticle

26 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

Fingerprint Dive into the research topics of 'How myasthenia gravis alters the safety factor for neuromuscular transmission'. Together they form a unique fingerprint.

Cite this