Journal
NEUROPHARMACOLOGY
Volume 53, Issue 7, Pages 881-889Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2007.08.018
Keywords
lithium Na+ channel; Ca2+ channel; catecholamine secretion; bipolar disorders; adrenal chromaffin cells
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Lithium has been proven to be effective in the therapy of bipolar disorder, but its mechanism of pharmacological action is not clearly defined. We examined the effects of lithium on voltage-dependent Na+ channels, nicotinic acetylcholine receptors, and voltage-dependent Ca2+ channels, as well as catecholamine secretion in cultured bovine adrenal chromaffin cells. Lithium chloride (LiCl) reduced veratridine-induced Na-22(+) influx in a concentration-dependent manner, even in the presence of ouabain, an inhibitor of Na+, K+-ATPase. Glycogen synthase kinase-3 (GSK-3) inhibitors (SB216763, SB415286 or the GSK-3 inhibitor IX) did not affect veratridine-induced Na-22(+) influx, as well as inhibitory effect of LiCl on veratridine-induced Na-22(+) influx. Enhancement of veratridine (site 2 toxin)-induced Na-22(+) influx caused by alpha-scorpion venom (site 3 toxin), alpha-scorpion venom (site 4 toxin), or Ptychodiscus brevis toxin-3 (site 5 toxin), still occurred in the presence of LiCI in the same manner as in the control cells. LiCI also reduced veratridine-induced Ca-45(2+) influx and catecholamine secretion. In contrast, LiCI (<= 30 mM) had no effect on nicotine-induced Na-22(+) influx, Ca-45(2+) influx and catecholamine secretion, as well as on high K+-induced Ca-45(2+) influx and catecholamine secretion. Chronic treatment with LiCI at 100 mM (but not at :5 30 mM) significantly reduced cell viability in a time-dependent manner. These results suggest that lithium selectively inhibits Na+ influx thorough Na+ channels and subsequent Ca2+ influx and catecholamine secretion, independent of GSK-3 inhibition. (c) 2007 Elsevier Ltd. All rights reserved.
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