Inhibitors of membrane depolarization regulate acetylcholine receptor synthesis by a calcium-dependent, cyclic nucleotide-independent mechanism

The inhibition of membrane depolarization by tetrodotoxin or the local anesthetic benzocaine elevates the acetylcholine receptor levels in cultured myotubes. The elevated acetylcholine receptor levels are due to increased receptor synthesis rather than to decreased degradation. The effects of tetrodotoxin and benzocaine on acetylcholine receptor levels are not additive, and are not inhibited by exogenously added cyclic GMP analogues or by elevated intracellular levels of cyclic GMP. However, the stimulation of acetylcholine receptor levels by tetrodotoxin or benzocaine is reversed by the addition of the calcium ionophore A23187. In contrast, tetrodotoxin or benzocaine stimulated acetylcholine receptor synthesis beyond the maximal stimulation produced by cholera toxin. These results suggest that the inhibition of membrane depolarization elevates acetylcholine receptor synthesis by a calcium-dependent, cyclic nucleotide-independent mechanism.