Increases in muscle Ca2+ mediate changes in acetylcholinesterase and acetylcholine receptors caused by muscle contraction

Abstract

The synthesis of acetylcholinesterase (AcChoE; acetylcholine acetylhydrolase, EC 3.1.1.7) and of acetylcholine receptors (AcChoR) by cultured rat muscle fibers is influenced strongly by the level of muscle contractile activity. If fibers are grown in the presence of tetrodotoxin (TTX) to block spontaneous contraction, the total amount of AcChoE decreases markedly, as does the percentage of AcChoE assembled as the collagen-tailed presumed synaptic form of the enzyme. Under these conditions, however, the number of AcChoR increases. We demonstrate here that each effect of TTX can be prevented by treating the muscle cells with the calcium ionophore A23187. Thus, cells treated with A23187 and TTX have 30- to 40-fold higher levels of collagen-tailed AcChoE and lower levels of AcChoR by a factor of 4-5 than do cells grown in TTX alone. These results suggest that an increase in muscle cytoplasmic Ca2+ mediates the known effects of muscle contraction on these cholinergic macromolecules.