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Mechanism of action of lithium on acetylcholine receptor metabolism in skeletal muscle. (Reannouncement with new availability information)

Technical Report ·
OSTI ID:117861
Changes in the levels of cations within skeletal muscle are thought to mediate the neural regulation of turnover of extrajunctional acetylcholine receptors (AChRs). The authors have used lithium as a probe of these cation influences because of its similarity to calcium and other ions. In the present experiments they studied the mechanisms of action of lithium on AChR metabolism in cultured mammalian skeletal muscle. They measured the effects of lithium on AChR turnover (using alpha-bungarotoxin binding), and evaluated the similarity of lithium and calcium in producing their effects on AChR metabolism in muscle. Their results provide insight into the mechanisms of action of lithium and the cellular processes controlling AChR metabolism in muscle. Lithium reduces the number of AChRs in skeletal muscle in vitro to a degree similar to that which the authors previously reported in vivo. Lithium appears to enter cells via both sodium and calcium channels. It then produces its effect on levels of AChRs primarily by selectively reducing AChR synthesis and insertion into the surface membrane. Lithium induces this change in AChR metabolism in a manner resembling neural and calcium-mediated effects on AChRs. Phosphoinositide pathways may be involved in the lithium-induced effects. Further analysis of the effects of lithium on AChR turnover should provide new information about the mechanisms underlying the cellular control of receptor metabolism.
Research Organization:
Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Neurology
OSTI ID:
117861
Report Number(s):
AD-A--246092/1/XAB; CNN: Contract DAMD17-85-C-5069
Country of Publication:
United States
Language:
English