Myasthenia gravis (MG), a postsynaptic disorder of neuromuscular transmission, is characterized by exertional weakness which is improved with rest. Uniquely there is a predilection for weakness of the ocular and oculorotatory muscles. Appropriate immunosuppressive therapy may be delayed because of the restricted presentation of this disorder. The cause of this differential weakness is not known. Speculation and some data suggests that the safety factor (the susceptibility to functional weakness) of neuromuscular transmission is reduced in muscles of ocular motility. In order to elucidate those physiologic factors which might account for this variability the quantal components and kinetics of neurotransmitter release will be examined in representative ocular, respiratory and appendicular muscles from animals with """"""""high"""""""" and """"""""low"""""""" safety factors. The characteristics of synaptic transmission will be examined in animals with experimental autoimmune myasthenia gravis (EAMG) to determine whether there is a predilection of attack for the ocular muscles. Single fiber electromyography, a clinical neurophysiological index known to correlate with the clinical course of MG, will be examined in these muscles and correlated with the intracellular physiology of neuromuscular transmission. The density of acetylcholine receptors in these muscles of animals with """"""""high"""""""" and """"""""low"""""""" safety factors will be determined to see if differences do exist. Comparisons will be made with animals with EAMG to determine if there is a predilection of attack and finally the characteristics of myasthenic antibody binding to these receptors will be examined to see if there is a specificity of ocular antibody to ocular muscle.
| Protti, M P; Manfredi, A A; Straub, C et al. (1990) CD4+ T cell response to the human acetylcholine receptor alpha subunit in myasthenia gravis. A study with synthetic peptides. J Immunol 144:1276-81 |
