Metabolic stabilization of endplate acetylcholine receptors regulated by Ca2+ influx associated with muscle activity.
During formation of the neuromuscular junction, acetylcholine receptors in the endplate membrane become metabolically stabilized under neural control, their half-life increasing from about 1 day to about 10 days. The metabolic stability of the receptors is regulated by the electrical activity induced in the muscle by innervation. 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 metabolic 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.
Rotzler
S
S
Department of Physiology, University of Basel, Switzerland.
Schramek
H
H
Brenner
H R
HR
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D006207:Half-Life; D008297:Male; D009045:Motor Endplate / Q000378:metabolism*; D009121:Muscle Denervation; D009132:Muscles / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009924:Organ Culture Techniques; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D011950:Receptors, Cholinergic; D012433:Ryanodine; D000001:Calcimycin; D013779:Tetrodotoxin; C045796:SAN 202791; D011188:Potassium; D002118:Calcium