title: Myasthenia gravis and myasthenic syndrome: simulation of twitch strength with or without therapy.
abstract: To examine the quantitative relationship between indirectly evoked twitch and decreases in the number of either postsynaptic receptors or acetylcholine molecules released by a single stimulus, we studied these variables in a computer-simulated model of neuromuscular transmission. Twitch strength decreased if the number of receptors decreased to below 30% of normal or the number of acetylcholine molecules released by a stimulus decreased to below 80%. Inhibition of acetylcholine hydrolysis to 50% restored twitch strength in the presence of a decreased number of receptors. However, twitch strength was more easily restored to normalcy by augmenting the release of acetylcholine, if the release was diminished by disease. The simulations mimic the clinically known therapeutic outcomes in certain disorders of neuromuscular transmission. These results provide useful quantitative insights into the relationship between acetylcholine receptors or the stimulus-induced release of acetylcholine and muscle function in myasthenia gravis or Lambert-Eaton myasthenic syndrome.
authors.affiliation: Department of Anesthesiology, Medical University of Ohio, 3000 Arlington Avenue, Toledo, Ohio 43614-2598, USA. vnigrovic@meduohio.edu
authors.forename: Vladimir
authors.initials: V
authors.lastname: Nigrovic
authors.forename: Anton
authors.initials: A
authors.lastname: Amann
authors.forename: Shashi
authors.initials: S
authors.lastname: Bhatt
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003198:Computer Simulation; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects*; D009157:Myasthenia Gravis / Q000188:drug therapy* / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000378:metabolism
chemical_list: D002800:Cholinesterase Inhibitors; D011950:Receptors, Cholinergic; D000109:Acetylcholine