Factors influencing degradation of extrajunctional acetylcholine receptors in skeletal muscle.

During development and after both denervation and reinnervation in adult mammalian skeletal muscle, the level of acetylcholine (ACh) receptors in the extrajunctional membrane undergoes wide variation. We have determined the rate of extrajunctional receptor degradation in denervated muscles in organ culture under a variety of conditions by measuring the rate at which alpha-bungarotoxin bound to the receptors is degraded. Direct electrical stimulation of muscles for several days dramatically reduced the levels of extrajunctional ACh sensitivity, and also reduced the rate of receptor degradation. Since the effect of activity on the rate of receptor degradation is in the opposite direction of the observed change in receptor levels, we conclude that activity must also decrease the rate of receptor synthesis. Receptor degradation was also examined in muscles at various times after denervation. The half-time of degradation increased from approximately 7 hr at 2-5 days after denervation to approximately 14 hr at 10-14 days. Hypophysectomy, which decreases the average rate of protein degradation in muscle, also decreased the rate of extrajunctional receptor degradation, but thyroxine, which restores the normal rate of overall protein breakdown in hypophysectomized animals, did not affect receptor breakdown. Since hypophysectomy did not increase the level of extrajunctional ACh receptors, it must also affect ACh receptor synthesis.