Effects of myasthenic immunoglobulins and of prednisolone on spontaneous miniature end-plate potentials in mouse diaphragms

After injection with myasthenic immunoglobulins (Ig) isolated from sera of patients, mice develop myasthenic symptoms. The extent to which postsynaptic receptors are altered by this reaction was investigated by measuring the amplitude and time course of spontaneous miniature end-plate potentials (SEPPs) recorded extracellulary from muscle fibers of untreated and pretreated mice. Relative to the controls, the average SEPP amplitude was decreased 44% in myasthenic Ig-treated fibers, and the time constant (τ) of decay of the SEPP increased slightly but significantly by 16%. A single exponential very accurately describes the decay of the SEPP in both untreated and treated fibers, indicating that the functional receptors were homogeneously affected by myasthenic Ig. The reduction of the amplitude of the SEPP by myasthenic Ig can probably be atributed to the decreased density of receptors reported in previous studies. Myasthenia gravis is often treated with corticosteriods. Prednisolone (10 −3 mol/liter) applied to control preparations decreased SEPP amplitude 42%, and τ 12%, on the average. Both these effects of prednisolone were more pronounced in fibers pretreated with myasthenic Ig; in particular, τ was shortened 26% in pretreated fibers. These findings established that in addition to its presynaptic actions evident from the observed increase in frequency of SEPPs, prednisolone also had effects on the postsynaptic receptors. No evidence for improved neuromuscular transmission due to direct action of prednisolone was obtained. The reduction in amplitude and duration of postsynaptic currents by prednisolone may explain the transitory aggravation of myasthenic symptoms often observed at the start of treatment with corticosteroids.