SUPERSENSITIVITY TO ANTICHOLINESTERASES OF AN ISOLATED NERVE-MUSCLE PREPARATION FROM HEREDITARILY DYSTROPHIC MICE

¹ Department of Therapeutical Chemistry, Istituto Superiore di Sanita, Rome, Italy

Hereditarily muscular dystrophic mice and their normnal litter-mates were used to study the response of isolated peroneus nerve-muscle preparations to two types of anticholinesterases. Physostigmine (1.2 x 10^-7 M) and tetraethylpyrophosphate (3.0 to 10.0 x 10^-7 M) induced violent spontaneous twitching in dystrophic but not in normal preparations. Electrical stimulation was not required in order to initiate fasciculation in the presence of anticholinesterases. A variety of drugs was found which would inhibit the spontaneous twitching induced by physostigmine without blocking neuromuscular transmission: d-tubocurarine (1.6 x 10^-7 M), trihexyphenidyl (9.2 x 10^-6 M), physostigmine (2.0 x 10^-5 M), atropine (2.6 to 5.2 x 10^-5 M) and procaine (3.6 to 6.5 x 10^-5 M). Tetraethylpyrophosphate, at the concentration required to initiate fasciculation in dystrophic peronei, subsequently inhibited twitching without blocking neuromuscular transmission. The latter inhibitory action could be dissociated from the stimulatory effect by washing the preparation within 1 minute after addition of TEPP (1.0 x 10^-5 M), in which case twitching was initiated within 30 seconds and continued for at least 2.5 hours. The results confirm that a defect exists in the cholinergic mechanism of the neuromuscular junction of dystrophic mice.