EFFECTS OF ANTIBODIES TO TORPEDO ACETYLCHOLINE-RECEPTOR ON THE ACETYLCHOLINE RECEPTOR IONIC CHANNEL COMPLEX OF TORPEDO ELECTROPLAX AND RABBIT INTERCOSTAL MUSCLE

An electrophysiological, biochemical, and ultrastructural study of the acetylcholine (ACh) receptor-ionic channel complex was undertaken in electric organ membranes from the electric ray, Torpedo ocellata, and intercostal muscle of the rabbit. Rabbits immunized with receptor purified from Torpedo ocellata were paralyzed as is characteristic of experimental autoimmune myasthenia gravis. Incubation of Torpedo membranes with antisera from six paralyzed rabbits, but not control rabbits, resulted in inhibition of [3H]ACh and [125I]α-BGT binding by 19 to 95% and 43 to 86%, respectively, and did not significantly affect the binding of [3H]H12-HTX. Anti-ACh-receptor antibodies bound to Torpedo microsacs were identified in electron micrographs by specific binding of ferritin-labeled goat anti-rabbit antibodies. Treatment of Torpedo microsacs with ACh-receptor antisera from rabbits inhibited their carbamylcholine-induced 22Na efflux, which would suggest direct effect of the antibodies on Torpedo ACh-receptor function. However, addition of the same anti-Torpedo-ACh-receptor antisera for 240 min to inter-costal muscles of rabbits produced only a small reduction in the amplitude of the response to microiontophoretically applied ACh, miniature end-plate potentials, and end-plate potentials. It is suggested that the muscle weakness observed in rabbits immunized with Torpedo ACh-receptor protein may be due to time-requiring action on receptors such as their accelerated degradation, and the amount of antimuscle receptor in rabbit antisera against Torpedo receptor may be too small. © 1979.