Evidence for an Upregulation of Acetylcholine Receptor Messenger Subunits Triggered by Antibody-Mediated Receptor Internalization in Human Myasthenia Gravis Muscles

The muscle nicotinic acetylcholine receptor (nAChR) is a well-characterized, ligand-gated ion channel of 270 kD that forms a pentameric complex of four homologous subunits with a molar stoichiometry of α2, β, e, δ [1, 2]. In mammalian muscle, regulation of nAChR subunit mRNAs and the distribution of nAChRs along the fiber are developmentally regulated. Transcript levels increase during myogenic differentiation and are repressed during muscle innervation; denervation results in re-accumulation [3]. The nAChR e and γ-subunits are also under developmental control, with expression of two types of channels in mammals. In early embryonic stages and upon denervation, a low-conductance, long-open-time channel composed of α, β, δ and γ-subunits and distributed throughout the fiber length predominates [4], whereas in adult fibers, a high-conductance, brief-open-time channel containing α, β, δ and e-subunits is expressed exclusively at the motor-endplate [5].