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Yanagita T, Maruta T, Nemoto T, Uezono Y, Matsuo K, Satoh S, Yoshikawa N, Kanai T, Kobayashi H, Wada A: Chronic lithium treatment up-regulates cell surface Na (V) 1.7 sodium channels via inhibition of glycogen synthase kinase-3 in adrenal chromaffin cells: enhancement of Na (+) influx, Ca (2+) influx and catecholamine secretion after lithium withdrawal. Neuropharmacology. 2009 Sep;57(3):311-21. Epub 2009 May 30.
In cultured bovine adrenal chromaffin cells expressing Na (V) 1.7 isoform of voltage-dependent Na (+) channels, we have previously reported that lithium chloride (LiCl) inhibits function of Na (+) channels independent of glycogen synthase kinase-3 (GSK-3) (Yanagita et al., 2007). Here, we further examined the effects of chronic lithium treatment on Na (+) channels. LiCl treatment (1-30 mM, > or = 12 h) increased cell surface [(3) H] saxitoxin ([(3) H] STX) binding by approximately 32% without altering the affinity of [(3) H] STX binding. This increase was prevented by cycloheximide and actinomycin D. SB216763 and SB415286 (GSK-3 inhibitors) also increased cell surface [(3) H] STX binding by approximately 31%. Simultaneous treatment with LiCl and SB216763 or SB415286 did not produce an increased effect on [(3) H] STX binding compared with either treatment alone. LiCl increased Na (+) channel alpha-subunit mRNA level by 32% at 24 h. LiCl accelerated alpha-subunit gene transcription by 35% without altering alpha-subunit mRNA stability. In LiCl-treated cells, LiCl inhibited veratridine-induced (22) Na (+) influx as in untreated cells. However, washout of LiCl after chronic treatment enhanced veratridine-induced (22) Na (+) influx, (45) Ca (2+) influx and catecholamine secretion by approximately 30%. Washout of LiCl after 24 h treatment shifted concentration-response curve of veratridine upon (22) Na (+) influx upward, without altering its EC (50) value. Ptychodiscus brevis toxin-3 allosterically enhanced veratridine-induced (22) Na (+) influx by two-fold in untreated and LiCl-treated cells. Whole-cell patch-clamp analysis indicated that I-V curve and steady-state inactivation/activation curves were comparable between untreated and LiCl-treated cells. Thus, GSK-3 inhibition by LiCl up-regulated cell surface Na (V) 1.7 via acceleration of alpha-subunit gene transcription, enhancing veratridine-induced Na (+) influx, Ca (2+) influx and catecholamine secretion. |
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