Modulation of acetylcholine receptor by antibody against the receptor

Abstract

Antibody against acetylcholine receptor induced an increase in the rate of degradation of acetylcholine receptors on a mouse [muscle] cell line (BC3H-1) and cultured rat skeletal muscle. The increased rate of degradation resulted in a lowered density of acetylcholine receptors on muscle membrane and a lowered sensitivity to iontophoretically applied acetylcholine. The modulation of acetylcholine receptor was energy, temperature and time dependent and may be related to antigenic modulation found in other systems. Acetylcholine noise analysis demonstrated that antibody against acetylcholine receptor reduced the channel mean conductance and mean open time slightly. It was concluded that antibody bound to the acetylcholine receptor, impaired its function and induced receptor degradation. This resulted in a lowered density of acetylcholine receptor and a lowered sensitivity to acetylcholine. Patients with myasthenia gravis have antibodies to their acetylcholine receptor in their serum. Antigenic modulation of receptor in the muscle of patients with myasthenia gravis could contribute to the observed decrease in amplitudes of miniature endplate potentials and in muscle acetylcholine sensitivity, and the symptoms of muscular weakness.