Depolarization, desensitization and the effects of tubocurarine and neostigmine in cultured skeletal muscle

The actions of acetylcholine, carbachol, d-tubocurarine and neostigmine were studied in cultures of chick embryo skeletal muscle. Both agonists produced a rapid, concentration-dependent depolarization. The depolarization to a given concentration was greater in older cells with higher resting membrane potentials, but the response percent of resting potential was constant throughout development. Despite continued presence of the agonists, depolarization was not maintained, the membrane potential returning to control level in about 15 min. The rate of recovery increased with age of cells and concentration of agonist. Specific desensitization of acetylcholine receptors was demonstrated. Cross-desensitization between acetylcholine and carbachol was observed, but receptor desensitization was unaffected by potassium-induced depolarization. d-Tubocurarine competitively antagonised the cholinomimetic response. Neostigmine did not potentiate responses to low concentrations of acetylcholine, but did, itself, cause some desensitization. The results indicate that the acetylcholine receptors of cultured skeletal muscle are similar in many respects to adult nicotinic receptors.