title: How myasthenia gravis alters the safety factor for neuromuscular transmission.
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.
authors.affiliation: Neurology Service, Louis Stokes Department of Veterans Affairs Medical Center, Departments of Neurology and Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States. robert.ruff1@va.gov
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ruff
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
mesh_terms: D000328:Adult; D000818:Animals; D020916:Conotoxins / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D009045:Motor Endplate / Q000187:drug effects / Q000503:physiopathology*; D009157:Myasthenia Gravis / Q000473:pathology* / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*
chemical_list: D020916:Conotoxins; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; D015222:Sodium Channels; C046101:conotoxin GIII