Figure 22-8 Distribution of acetylcholine receptors in developing adult, mature, and denervated muscle. A and B, In the early fetal stage, mononucleated myoblasts, derived from the mesoderm, fuse to form multinucleated myotubes. The γ-subunit-containing immature acetylcholine receptors are scattered throughout the muscle membrane. C, As the nerve makes contact with muscle, clustering of the receptors occurs at the synapse and is associated with some loss of extrasynaptic receptors. D, Maturation of the junction is said to occur when epsilon-subunit-containing receptors replace the γ-subunit-containing receptors. Even mature muscle is multinucleated, but it is devoid of extrasynaptic nuclei. E, Denervation or another pathologic state (e.g., burns, immobilization, chronic muscle relaxant therapy, sepsis) leads to re-expression of the γ-subunit receptor at the junctional and the extrajunctional areas. The latter changes are potentially reversible.