Corticosteroids and neuromuscular transmission: Electrophysiological investigation of the effects of prednisolone on normal and anticholinesterase-treated neuromuscular junction

Abstract

The effect of prednisolone on indirectly stimulated rat muscle twitch was investigated at normal and prostigmine-treated neuromuscular junctions. In vivo, predenisolone up to 150 mg/kg body weight did not affect twitch contraction in normal animals. In neostigmine-pretreated animals, however, doses between 12.5 and 90 mg/kg could entirely abolish the anticholinesterase-induced twitch augmentation. In vitro, prednisolone produced a depressant effect on the twitch of a normal phrenic nerve diaphragm preparation which could amount to 20%. When the preparation was pretreated with neostigmine the augmented twitch could be depressed by 10⁻³ to 10⁻⁶ mol/l prednisolone to levels below the untreated control. Part of this effect is owing to a suppression of the neostigmine-induced, stimulus-bound repetitive firing of the motor nerve terminals, but to explain the full effect a further inhibitory action on neuromuscular transmission must be assumed. The latter could be accounted for by a depolarizing interaction of prednisolone and neostigmine on the nerve terminals resulting in conduction block. An action of prednisolone on postsynaptic receptors could also be considered. Such effects of the glucocorticoid might contribute to the exacerbation of muscular weakness occasionally observed in patients with myasthenia gravis at the beginning of steroid therapy.