Tunicamycin increases desensitization of acetylcholine receptors in cultured mouse muscle cells.

Whole-cell currents activated by acetylcholine (AcCho) were recorded in C2 mouse myotubes before and after prolonged treatment with tunicamycin, an inhibitor of glycosylation. In control cells the AcCho-induced currents decayed slowly even in the continuous presence of AcCho. After 24 hr of treatment with tunicamycin AcCho still elicited currents, but their size was significantly reduced and their decay was greatly accelerated. The binding of 125I-labeled alpha-bungarotoxin, a specific and irreversible antagonist of muscle AcCho receptors, was greatly reduced after tunicamycin treatment, and an equivalent reduction was observed after a long-lasting application of the AcCho agonist carbachol. We suggest that, after inhibition of glycosylation by tunicamycin, AcCho receptors are expressed correctly on the plasma membrane but these receptors desensitize more rapidly and are less efficient in binding alpha-bungarotoxin.