Metabolic stabilization of endplate acetylcholine receptors regulated by Ca²⁺ influx associated with muscle activity

Abstract

DURING formation of the neuromuscular junction, acetylcholine receptors in the endplate membrane become matabolically stabilized under neural control, their half-life increasing from about 1 day to about 10 days (see ref. 1 for review). The metabolic stability of the receptors is regulated by the electrical activity induced in the muscle by innervation^2–4 We report here that metabolic stabilization of endplate receptors but not of extrajunctional receptors can be induced in the absence of muscle activity if muscles are treated with the calcium ionophore A23187. Acetylcholine receptor stabilization was also induced by culturing non-stimulated muscle in elevated K⁺ with the Ca²⁺ channel activator (+)-SDZ202-791. Conversely, activity-dependent receptor stabilization is prevented in muscle stimulated in the presence of the Ca²⁺ channel blockers (+)-PN200-110 or D-600. Treatment of muscles with ryanodine, which induces Ca²⁺ release from the sarcoplasmic reticulum in the absence of activity, does not cause stabilization of junctional receptors. Evidently, muscle activity induces meta- bolic acetylcholine receptor stabilization by way of an influx of Ca²⁺ ions through dihydropyridine-sensitive Ca²⁺ channels in the endplate membrane, whereas Ca²⁺ released from the sarcoplasmic reticulum is ineffective in this developmental process.