How myasthenia gravis alters the safety factor for neuromuscular transmission

• Published in: Journal of neuroimmunology 2008-09, Vol.201, p.13-20
• Main Authors: Ruff, Robert L, Lennon, Vanda A
• Format: Article
• Language: English
• Subjects: Acetylcholine receptor; Action potential threshold; Adult; Allergy and Immunology; Animals; Conotoxins - pharmacology; Humans; Immunoglobulin G - pharmacology; In Vitro Techniques; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Middle Aged; Motor Endplate - drug effects; Motor Endplate - physiopathology; Myasthenia gravis; Myasthenia Gravis - pathology; Myasthenia Gravis - physiopathology; Neurology; Neuromuscular Junction - drug effects; Neuromuscular Junction - pathology; Neuromuscular Junction - physiopathology; Passively transferred MG; Patch-Clamp Techniques - methods; Rats; Rats, Inbred Lew; Receptors, Cholinergic - immunology; Safety factor; Sodium channels; Sodium Channels - drug effects; Sodium Channels - physiology
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2008.04.038

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.