Mechanism of action of lithium on acetylcholine receptor metabolism in skeletal muscle.
Changes in the levels of cations within skeletal muscle are thought to mediate the neural regulation of turnover of extrajunctional acetylcholine receptors (AChRs). We have used lithium as a probe of these cation influences because of its resemblance to calcium and other ions. In the present experiments we studied the mechanism of action of lithium on AChR metabolism in cultured mammalian skeletal muscle. We measured the effects of lithium on AChR turnover (using [125I]alpha-bungarotoxin binding), and evaluated the resemblance of lithium and calcium in producing their effects on AChR metabolism. Our 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 we 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.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D007294:Inositol / Q000494:pharmacology; D008094:Lithium / Q000378:metabolism / Q000494:pharmacology*; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism
D011950:Receptors, Cholinergic; D000001:Calcimycin; D007294:Inositol; D003994:Bucladesine; D008094:Lithium; D002118:Calcium