Intracellular acetylcholine receptors in skeletal muscles of the adult rat

We have examined the localization and numbers of acetylcholine receptors (AChRs) within adult mammalian skeletal muscle using ¹²⁵I-α-bungarotoxin (¹²⁵I-α-BuTx). Intracellular AChRs were exposed to ¹²⁵I-α-BuTx by permeabilizing the muscle membrane with the detergent saponin. Our results show that, in muscles of young adult rats, internal AChRs occur in a number and pattern of distribution similar to that for surface membrane AChRs. Internal AChRs are found only in perijunctional regions of normally innervated muscles, but they appear all along the length of muscle fibers after denervation. A minority of internal AChRs may be newly synthesized AChRs en route to insertion in the surface membrane; however, most internal AChRs appear to be antigenically different from and to behave independently of surface membrane AChRs. With increasing age, internal AChRs decline in number, while surface AChRs remain relatively constant. In older animals, internal AChRs may reappear in muscles that have undergone degeneration and regeneration. We conclude that a significant proportion of AChRs in skeletal muscle may be intracellular. Internal AChRs are a useful marker for young muscle cells. Their distribution may provide information about the intracellular pathways of AChR metabolism.