Abstract. We have studied the formation of acetylcholine receptor (AChR) clusters and the behavior of myonuclei in rat and chick skeletal muscle cells grown in cell culture. These cells were treated with a factor derived from Torpedo electric tissue extracellular matrix, which causes a large increase in their number of AChR clusters. We found that these clusters were located preferentially in membrane regions above myonuclei. This cluster-nucleus colocalization is explained by our finding that most of the nuclei near clusters remain relatively stationary, while most of those away from clusters are able to translocate throughout the myotube. In some cases, clusters clearly formed first, then nuclei migrated underneath and became immobilized. If clustered AChRs later dispersed, their associated nuclei resumed moving. These results suggest that AChR clustering initiates an extensive cytoskeletal rearrangement that causes the subcluster localization of organelles, potentially providing a stable source of newly synthesized AChRs for insertion into the cluster.

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During nerve-muscle synapse formation, acetylcholine receptors become localized and modified to allow efficient transfer of information from nerve to muscle. In this paper we summarize our studies on two aspects of receptor modulation--their concentration at synaptic sites and their ability to desensitize in response to prolonged application of agonist. We demonstrate that receptor localization is a complex event which extensively reorganizes the structure of the junctional region. This allows the subsequent influences of contraction to be exerted differently in junctional and extrajunctional regions. We indicate that increases in muscle cell Ca2+ appear to mediate some of the effects of muscle contraction and suggest how regulation of Ca2+ levels may specify junctional and extrajunctional differences. Finally, we discuss the role of receptor phosphorylation in determining the rate of desensitization.