How myasthenia gravis alters the safety factor for neuromuscular transmission.
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.
Ruff
Robert L
RL
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
Lennon
Vanda A
VA
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*
D020916:Conotoxins; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; D015222:Sodium Channels; C046101:conotoxin GIII