CONGENITAL MYASTHENIC SYNDROMES .2. SYNDROME ATTRIBUTED TO ABNORMAL INTERACTION OF ACETYLCHOLINE WITH ITS RECEPTOR

A 21-year-old woman had myasthenic symptoms since birth that responded poorly to anticholinesterase therapy. Tests for acetylcholine recepto r (AChR) antibodies were negative. An intercostal muscle specimen was obtained to investigate the character of the neuromuscular transmissio n defect. There were no immune deposits at the endplates. The quantal content of the endplate potential was normal. Miniature endplate poten tials and currents were very small, but the number of AChR per endplat e was normal. On electron microscopy, the synaptic vesicles were of no rmal size, the junctional folds were intact, and the density and distr ibution of AChR on the folds was normal. The kinetic properties of ACh R were studied by analysis of acetylcholine (ACh)-induced current nois e. The mean single channel conductance was normal. The noise power spe ctrum was abnormal, containing two components of different time course . This could result from an abnormal interaction of ACh with AChR, or from two populations of AChR at the endplate. The second possibility i s unlikely because if two populations of AChR were present at the endp late, then both would have to have low conductance to explain the smal l miniature endplate current, but the average conductance of the chann els that did open was normal. (C) 1993 John Wiley & Sons, Inc.