Altered TRPC7 gene expression in bipolar-I disorder

Background: As altered storage-operated calcium (Ca2+) entry (SOCE) may aff ect Ca2+ homeostasis in bipolar disorder (BD), we determined whether change s occur in the expression of TRPC7 and SERCA2s, proteins implicated or know n to be involved in SOCE, in B lymphoblast cell lines (BLCLs) from BD-I pat ients and comparison subjects. Methods: mRNA levels were determined in BLCL lysates from BD-I, BD-II, and major depressive disorder patients, and heal thy subjects by comparative reverse transcriptase-polymerase chain reaction , and BLCL basal intracellular Ca2+ concentration ([Ca2+](B)) was determine d by ratiometric spectrophotometry using Fura-2, in aliquots of the same ce ll lines, at 13-16 passages in culture. Results: TRPC7 mRNA levels were sig nificantly lower in BLCLs from BD-I patients with high BLCL [Ca2+](B) compa red with those showing normal [Ca2+](B) (-33%, p =.017) and with BD-II pati ents (-48%, p =.003), major depressive disorder patients (-47%, p =.049) an d healthy subjects (-33%, p =.038). [Ca2+]B also correlated inversely with TRPC7 mRNA levels in BLCLs from the BD-I group as a whole (r = -.35, p =.02 7). Conclusions: Reduced TRPC7 gene expression may be a trait associated wi th pathophysiological disturbances of Ca2+ homeostasis in a subgroup of BD- I patients. (C) 2001 Society of Biological Psychiatry.