We developed a modified anti-acetylcholine receptor (AChR) antibody (Ab) assay based on a radioreceptor assay and a calibration curve. We compared the analytical and clinical performances of this modified assay with those of the conventional anti-AChR Ab radioreceptor assay. Serum specimens were from patients with myasthenia gravis (MG) (n = 156) and from control subjects (n = 106). The modifie...

We trace the cause of congenital myasthenic syndromes in two patients to mutations in the epsilon subunit of the muscle acetylcholine receptor (AChR). Both patients harbour deletion of an asparagine residue in the epsilon subunit (epsilonN436del) at the C-terminus of the cytoplasmic loop linking the third (M3) and fourth (M4) transmembrane domains. The presence of a null mutation in the second ...

Embryonic Xenopus muscle cells grown in culture develop discrete patches of high acetylcholine receptor (AChR) density. By following identified muscle cells after staining with fluorescent alpha-bungarotoxin, we have found that many of these AChR patches survive in a fixed position for several days. For AChR patches on the lower surface of the cell (the surface apposed to the culture dish), mor...

The rate constants of acetylcholine receptor channels (AChR) desensitization and recovery were estimated from the durations and frequencies of clusters of single-channel currents. Diliganded-open AChR desensitize much faster than either unligandedor diliganded-closed AChR, which indicates that the desensitization rate constant depends on the status of the activation gate rather than the occupan...

The cellular mechanisms of degradation of a transmembrane protein, the acetylcholine receptor (AChR), have been examined in a mouse muscle cell line, BC3H-1. The halftime of degradation of cell surface receptors labeled with [125I] alpha-Bungarotoxin ([125I] alpha-BuTx) is 11-16 h. Leupeptin, a lysosomal protease inhibitor, slows the degradation rate two- to sixfold, depending on the concentrat...

Specific isoforms of laminin (LN) are concentrated at neuromuscular junctions (NMJs) where they may participate in synaptic organization or function. In myotubes from C2 cells, LN is concentrated within the majority of spontaneous acetylcholine receptor (AChR) aggregates. Neural agrin substantially increases this colocalization, suggesting that agrin can recruit LN into AChR aggregates. Additio...

Several studies have suggested that the autoantibodies (autoAbs) against muscle acetylcholine receptor (AChR) of myasthenia gravis (MG) patients are the main pathogenic factor in MG; however, this belief has not yet been confirmed with direct observations. Although animals immunized with AChR or injected with anti-AChR monoclonal Abs, or with crude human MG Ig fractions exhibit MG symptoms, the...

BACKGROUND Arthrogryposis multiplex congenita (AMC) is defined as nonprogressive congenital contractures that generally result from lack of fetal movement in utero. AMC is a feature of many congenital disorders caused by genetic, environmental, or other factors. One rare cause of AMC is maternal myasthenia gravis (MG). This is an autoimmune disorder, caused by antibodies to the nicotinic acetyl...

We examined the effects of denervation on clusters of nicotinic acetylcholine receptors (AChRs) on autonomic neurons in the frog heart using immunofluorescence techniques and laser scanning confocal microscopy. We showed previously that normally innervated neurons have both large, brightly stained AChR clusters and small, dim AChR clusters. A majority (80%) of the large/bright AChR clusters are...

Neuromuscular junctions (NMJs) normally form in the central region of developing muscle. In this process, agrin released from motor neurons has been considered to initiate the formation of synaptic acetylcholine receptor (AChR) clusters (neurocentric model). However, in muscle developing in the absence of nerves and thus of agrin, AChR clusters still form in the muscle center. This raises the p...