title: Factors contributing to failure of neuromuscular transmission in myasthenia gravis and the special case of the extraocular muscles.
abstract: Acetylcholine receptors (AchRs) and Na(+)  channels (NaChs) are concentrated on neuromuscular junction (NMJ) postsynaptic folds; both are depleted in myasthenia gravis (MG), reducing the safety factor (SF) for neuromuscular transmission, especially in extraocular muscles (EOM). Studies of human myasthenic nerve-muscle preparations indicate that loss of endplate AChRs accounts for 59%, and NaChs for 40%, of SF reduction. Rodent models of MG indicate that NaChs and AChRs losses are due to complement-mediated destruction of postsynaptic folding. Saccades in MG show stereotyped, conjugate initial components, similar to normal but different from early disconjugacy with ocular nerve palsies. Loss of AChRs, NaChs, and postsynaptic folding all contribute to SF reduction in MG. EOM seem more susceptible to MG because of poor postsynaptic folding, lower baseline SF, and lower levels of intrinsic complement inhibitors. Initial conjugacy of saccades in MG reflects selective sparing of neuromuscular transmission of fast, pale global fibers, which have better developed postsynaptic folding.
authors.affiliation: Neurology Service, Veterans Affairs Medical Center and Case Medical Center, Cleveland, Ohio, USA. Alessandro.Serra@UHhospitals.org
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serra
authors.forename: Robert
authors.initials: R
authors.lastname: Ruff
authors.forename: Henry
authors.initials: H
authors.lastname: Kaminski
authors.forename: R John
authors.initials: RJ
authors.lastname: Leigh
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D005133:Eye Movements / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009045:Motor Endplate / Q000503:physiopathology; D009157:Myasthenia Gravis / Q000503:physiopathology*; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000503:physiopathology / Q000648:ultrastructure; D009801:Oculomotor Muscles / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology*; D009802:Oculomotor Nerve / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011950:Receptors, Cholinergic / Q000502:physiology; D012438:Saccades / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D011950:Receptors, Cholinergic; D015222:Sodium Channels