title: 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.
abstract: 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.
authors.affiliation: Department of Pharmacology, Miyazaki Medical College, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan. yanagita@med.miyazaki-u.ac.jp
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yanagita
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Maruta
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nemoto
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Uezono
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Matsuo
authors.forename: Shinya
authors.initials: S
authors.lastname: Satoh
authors.forename: Norie
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kanai
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Wada
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D055550:Protein Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018692:Antimanic Agents; D015220:Calcium Channels; D002395:Catecholamines; D012333:RNA, Messenger; D015222:Sodium Channels; D012964:Sodium; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride; D002118:Calcium