Changes in the levels of acetylcholine receptors mediated by calcium concentration in the sarcoplasmic reticulum.
Regulation of the AChR level, assayed by 125I-alpha-bungarotoxin binding, was studied in chick skeletal muscles differentiated in cell culture. Variety of agents known to affect muscle contractions and calcium distribution were investigated. Synthesis of AChR is enhanced by treatment of myotubes with several drugs known to inhibit spontaneous activity, such as tetrodotoxin or D 600. In contrast, a reduction of AChR levels occurs due to prolonged treatment with caffeine or carbamylcholine. Sodium dantrolene which inhibits Ca2+ release from the sarcoplasmic reticulum, causes 90% elevation in the level of receptors when applied for 48 hr. Furthermore, in a combination of treatments with dantrolene and carbamylcholine, the effect of the last one is almost abolished. Similarly, in a combined treatment of D 600 together with caffeine, the last one is more dominant and reduces the level of the receptors, inspite of inactivity of the myotubes. These experiments support the idea that cytosolic Ca2+ acts as an information carrier to activate/inactivate the machinery of receptor synthesis. We conclude that muscle activity is not the main factor regulating AChR synthesis, but that intracellular Ca2+ released from the sarcoplasmic reticulum is a necessary mediator for the decline in AChR synthesis, whereas Ca2+ accumulation in SR exerts the opposite effect: enhancement of receptor synthesis.
Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
A
A
Shainberg
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Freud-Silverberg
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H
Brik
D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D003620:Dantrolene / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D007700:Kinetics; D009132:Muscles / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
D002038:Bungarotoxins; D011950:Receptors, Cholinergic; D005711:Gallopamil; D002110:Caffeine; D002217:Carbachol; D003620:Dantrolene; D002118:Calcium