Effects of lithium on synaptosomal Ca2+ fluxes.
Lithium is the primary treatment for mania, and it has been employed as a therapeutic agent in the treatment of a number of other conditions. In spite of its widespread clinical use, the specific mechanism by which lithium acts is still not known. Because lithium bears some chemical resemblance to Ca2+ and because it has been found to interfere with many Ca2+-dependent processes, we investigated the possibility that lithium can alter intracellular Ca2+ homeostasis by an effect on Ca2+ fluxes. When added in vitro to synaptosomes prepared from rat forebrains, lithium had no effect on 45Ca2+ influx mediated by fast or slow phase depolarization-dependent Ca2+ channels or by Na+/Ca2+ exchange. In vitro treatment with lithium also had no effect on ATP-dependent Ca2+ sequestration by mitochondria or synaptosomal endoplasmic reticulum. In contrast, 45Ca2+ influx in synaptosomes prepared from rats treated chronically with lithium was increased significantly relative to controls. The fact that chronic in vivo treatment with lithium affected synaptosomal Ca2+ flux whereas in vitro treatment did not is consistent with the time course of therapeutic effectiveness in man. The results suggest that lithium does not directly interact with synaptosomal Ca2+ flux, but rather may influence Ca2+ flux through an indirect mechanism following chronic treatment.
Koenig
M L
ML
Department of Pharmacology, University of Alabama, Birmingham 35294.
Jope
R S
RS
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002132:Calcium Radioisotopes; D011506:Proteins; D008094:Lithium; D012964:Sodium; D002118:Calcium