Auto-antibodies (Abs) directed to nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction cause loss of function and density of AChRs resulting in the disease, myasthenia gravis (MG). The AChRs are clustered, at high density, at the tips of the folds of the postsynaptic membrane in association with rapsyn and other synapseorganizing proteins. Rapsyn is non-covalently bound to the cytoplasmic portion of the beta subunit of the AChR and is essential for clustering in mammalian muscle cells. Rapsyn is also known to bind to the local anesthetic and anti-arrhythmic agent procainamide (PC). We have employed immunoblotting to test the serum from individuals with MG as well as from one patient with chronic PC-associated myopathy (CPAM) for Abs directed against the synapse-organizing proteins extracted from electrocytes of Torpedo californien. This reactivity was detected in the patient with CPAM as well as two out of 16 patients with MG, but was not present in controls. We have also induced experimental weakness in female Lewis rats by actively immunizing them with isolated synapseorganizing proteins. It is likely that anti-rapsyn Abs, as well as Abs directed against other synapse-organizing proteins, contribute to weakness and may account, at least in part, for the poor correlation between anti-AChR Abs and severity of weakness in some MG patients.
|Original language||English (US)|
|State||Published - 1996|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology