Raised cyclic-AMP and a small applied electric field influence differentiation, shape, and orientation of single...

The effects of the adenyl cyclase activator forskolin and of a small applied electric field on the differentiation, morphology, and orientation of processes from single Xenopus myoblasts has been studied. Forskolin promoted myoblast differentiation (elongation from spherical cells) and induced extra process growth, such that normally bipolar muscle cells possessed on average five or six processes. Both events appeared to depend on elevated levels of cyclic AMP, since they were mimicked by another adenyl cyclase activator, cholera toxin, and by two membrane-permeable analogues of cyclic AMP. By contrast, the forskolin analogue dideoxyforskolin, which does not elevate adenyl cyclase levels, was without effect. Forskolin-stimulated differentiation depended on new protein synthesis, while excess process production required both new protein synthesis and intact microfilaments. Both control and forskolin-treated myoblasts developed a long axis perpendicular to an applied electric field. In addition, many processes on forskolin-treated muscle cells turned to grow toward the cathode; untreated processes did not turn to either pole. Since this nerve-like orientation behavior was inhibited by a protein synthesis inhibitor, the expression of an integral component of galvanotropism may be stimulated by forskolin treatment and by raised cyclic AMP levels in myoblasts.