Altered TRPC7 gene expression in bipolar-I disorder

Background: As altered storage-operated calcium (Ca2+) entry (SOCE) may affect Ca2+ 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 Ca2+ concentration ([Ca2+]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 [Ca2+]B compared with those showing normal [Ca2+]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). [Ca2+]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 Ca2+ homeostasis in a subgroup of BD-I patients.