Altered TRPC7 gene expression in bipolar-I disorder.
BACKGROUND
As altered storage-operated calcium (Ca(2+)) entry (SOCE) may affect Ca(2+) homeostasis in bipolar disorder (BD), we determined whether changes occur in the expression of TRPC7 and SERCA2s, proteins implicated or known to be involved in SOCE, in B lymphoblast cell lines (BLCLs) from BD-I patients and comparison subjects.


METHODS
mRNA levels were determined in BLCL lysates from BD-I, BD-II, and major depressive disorder patients, and healthy subjects by comparative reverse transcriptase-polymerase chain reaction, and BLCL basal intracellular Ca(2+) concentration ([Ca(2+)]B) was determined by ratiometric spectrophotometry using Fura-2, in aliquots of the same cell lines, at 13-16 passages in culture.


RESULTS
TRPC7 mRNA levels were significantly lower in BLCLs from BD-I patients with high BLCL [Ca(2+)]B compared with those showing normal [Ca(2+)]B (-33%, p =.017) and with BD-II patients (-48%, p =.003), major depressive disorder patients (-47%, p =.049) and healthy subjects (-33%, p =.038). [Ca(2+)]B also correlated inversely with TRPC7 mRNA levels in BLCLs from the BD-I group as a whole (r = -.35, p =.027).


CONCLUSIONS
Reduced TRPC7 gene expression may be a trait associated with pathophysiological disturbances of Ca(2+) homeostasis in a subgroup of BD-I patients.
Yoon
I S
IS
Section of Biochemical Psychiatry, Centre for Addiction and Mental Health-Clarke Site, Toronto, Ontario, Canada.
Li
P P
PP
Siu
K P
KP
Kennedy
J L
JL
Macciardi
F
F
Cooke
R G
RG
Parikh
S V
SV
Warsh
J J
JJ
D000328:Adult; D001402:B-Lymphocytes; D001714:Bipolar Disorder / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000235:genetics*; D002460:Cell Line; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels
D015220:Calcium Channels; D007473:Ion Channels; D008565:Membrane Proteins; D050052:TRPC Cation Channels; C498501:TRPC7 protein, human; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D002118:Calcium