Chronic lithium treatment of B lymphoblasts from bipolar disorder patients reduces transient receptor potential channel 3 levels.
Chronic lithium treatment of B-lymphoblast cell lines (BLCLs) from bipolar-I disorder (BD-I) patients and healthy subjects ex vivo attenuates agonist- and thapsigargin-stimulated intracellular calcium (Ca(2+)) responses. As these findings suggest that chronic lithium treatment modifies receptor (ROCE) and/or store-operated Ca(2+) entry (SOCE) mechanisms, we determined whether chronic lithium treatment of BLCLs modified the expression of two members of the transient receptor potential channels (TRPC1 & 3), which participate in ROCE/SOCE. Chronic lithium treatment significantly reduced BLCL TRPC3 immunoreactivity (repeated-measures ANOVA, P=0.00005), with interaction effects of diagnosis (P=0.037) and sex (P=0.040). The lithium-induced decrease was greatest in BLCLs from female BD-I patients compared with those from healthy females (-27%) and with vehicle-treated BLCLs from female BD-I patients (-33%). However, lithium treatment did not affect TRPC1 and 3 mRNA levels, and TRPC1 immunoreactivity. Downregulation of TRPC3 may be an important mechanism by which lithium ameliorates pathophysiological Ca(2+) disturbances as observed in BD.
Andreopoulos
S
S
Laboratory of Cellular and Molecular Pathophysiology, Center for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
Wasserman
M
M
Woo
K
K
Li
P P
PP
Warsh
J J
JJ
D000328:Adult; D000704:Analysis of Variance; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D008094:Lithium / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D050052:TRPC Cation Channels
D007473:Ion Channels; D012333:RNA, Messenger; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D008094:Lithium