Two patients are described with a myasthenic syndrome that presented in early adult life. One patient had 2 asymptomatic first degree relatives with similar electrophysiological findings. Both patients had abnormal fatiguability, arm weakness being prominent; neither of them responded to anticholinesterase medication. An abnormal decrement at 3 Hz stimulation was present, and a single stimulus evoked a repetitive response. Electrophysiological studies on biopsied intercostal muscle showed miniature endplate potentials of normal amplitudes but with prolonged rise and decay times. Anticholinesterase staining (Case 1) was not reduced, and showed elongation of some endplates. Ultrastructural studies (Case 2) showed degeneration of junctional folds and diffusely thickened endplate basal lamina. Calcium deposits were not observed and myopathic changes were slight. The findings are consistent with a prolonged open time of the ACh-induced ion channel.

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SUMMARY1. Frog sartorius muscles were incubated in Ringer solutions with a raised K+ concentration (high K+) and then allowed to recover in medium with a normal K+ concentration. During the recovery period miniature end-plate potentials (m.e.p.p.s) were recorded with intracellular electrodes. In addition, the acetylcholine (ACh) released from muscles in the presence of high K+ was measured by a mass spectrometric method.2. Incubation in a high-K+ medium induced the appearance of giant miniature end-plate potentials (g.m.e

SUMMARY1. Skeletal muscles from rat, mouse and frog were incubated under different conditions and the amounts of acetylcholine (ACh) extractable from the tissue and released into the medium were determined by mass fragmentography. In some experiments measurements were made of the amounts of ACh ('bound' ACh) surviving in a muscle homogenate to which an excess of acetylcholinesterase had been added. In other experiments the membrane potentials, end-plate potentials (e.p.p.s), and miniature end-plate potentials (m.e.p.p.s) were studied.2. During incubation in Ringer medium the ACh content of the rat hemidiaphragm usually did not change, but after inhibition of cholinesterase by soman the ACh content rose gradually from about 100 to 150 pmol to a plateau of about 400 pmol after 4 h. A similar formation of 'surplus ACh' after cholinesterase inhibition was found in the mouse diaphragm, but not in the frog sartorius muscle.3. Surplus ACh accumulated predominantly in the end-plate region of the rat diaphragm. In muscles, 16-18 h after in vivo denervation, the capacity to form surplus ACh was decreased by more than 80 %.4. The amount of ACh diffusing from the resting hemidiaphragm into the incubation medium ('resting release') varied between 05 and 0-9 pmol min-' in different experiments; it remained at the same level during accumulation of surplus ACh. It was reduced by more than 80 % 16-18 h after denervation.5

Two cases of a newly recognized myasthenic syndrome were investigated (CPSC syndrome). The course of the disease was observed for periods of 6 and 3 years. In infancy, exacerbations of the symptoms occurred during febrile illness, but thereafter the clinical course was stable and the children appeared to be only slightly handicapped. Biopsies were taken from the intercostal muscle in both patients. Microelectrode studies revealed small Mepp amplitudes. Light microscopy demonstrated predominance of type I fibers and focal type-grouping. There was a lowered cholinesterase activity and frequent branching of preterminal axons. Electron microscopy revealed that there were few, if any, folds of the postsynaptic membrane and that there were no signs of degeneration. Methods for localization of acetylcholine receptors (AChR) revealed a deficiency and altered distribution of AChRs at these postsynaptic membranes and the occurrence of extrajunctional AChRs in some muscle fibers. It is concluded that the syndrome is a clinicopathological entity, characterized morphologically by a congenital paucity of secondary synaptic clefts (CPSC syndrome).