Adenylyl cyclase activity in clonally derived human myoblast cultures: evidence for myoblast heterogeneity

In vitro myogenesis recapitulates the programme of myogenesis in vivo. During the process of muscle differentiation, cAMP plays an important role in the control of gene expression and in the integration of metabolic functions. cAMP generation may be affected by drugs or hormones that interact with the membrane-bound enzyme adenylyl cyclase, including adrenergic agents and glucocorticoids. In this study, adenylyl cyclase activity was evaluated in membranes prepared from human clonally derived muscle cultures. In control cultures, there was considerable inter-clonal variation in basal, sodium-fluoride and forskolin-stimulated adenylyl cyclase activity. Cultures differed in their response to steroids: adenylyl cyclase activity was markedly enhanced in some clones, and was significantly inhibited in other clones. Pre-treatment of cultures with pertussis toxin indicated that the effects of steroids are mediated in part by modulation of G-protein activity. These findings indicate a substantial heterogeneity among myoblast clones with respect to the modulating effect of steroids on adenylyl cyclase activity. This observation may account for the conflicting reports of steroid effects on muscle in vitro, and may be of relevance to the understanding of possible transmembrane signalling alterations in muscle disease.