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Hyperactive intracellular calcium dynamics in B lymphoblasts from patients with bipolar I disorder

Tatiana Perova, Michael J. Wasserman, Peter P. Li, Jerry J. Warsh
DOI: http://dx.doi.org/10.1017/S1461145707007973 185-196 First published online: 1 March 2008

Abstract

Substantial evidence implicates abnormalities of intracellular calcium (Ca2+) dynamics in the pathophysiology of bipolar disorder (BD). However, the precise mechanisms underlying such disturbances are poorly understood. To further elaborate the nature of altered intracellular Ca2+ signalling dynamics that occur in BD, we examined receptor- and store-operated Ca2+ responses in B lymphoblast cell lines (BLCLs), which have been found in earlier studies to ‘report’ BD-associated disturbances. Basal Ca2+ concentrations ([Ca2+]B), and lysophosphatidic acid (LPA)- and thapsigargin-stimulated Ca2+ responses were determined in BLCLs from 52 BD-I patients and 30 healthy comparison subjects using fura-2, and ratiometric fluorometry. ANOVA revealed a significant effect of diagnosis, but not gender, on [Ca2+]B (F1,63=4.4, p=0.04) and the rate of rise (F1,63=5.2, p=0.03) of LPA-stimulated Ca2+ responses in BLCLs from patients compared with those from healthy subjects. A significant gender×diagnosis interaction on the LPA-induced rate of rise (F1,63=4.6, p=0.03) was accounted for by a faster rate of rise (97%) in BLCLs from BD-I males compared with healthy males but not in those from female patients compared with healthy females. A gender×diagnosis interaction in thapsigargin-evoked Ca2+ influx (F1,61=3.8, p=0.05) resulted from a significantly higher peak [Ca2+]influx (24%) in BLCLs from female compared with male patients. The results suggest more rapid LPA-stimulated Ca2+ responses occur in BLCLs from BD-I patients compared with controls, which are probably mediated, in part, by canonical transient receptor potential type 3 (TRPC3)-like channels. Additionally, this study highlights sex-dependent differences that can occur in the pathophysiological disturbances involved in BD.

Key words
  • Bipolar I disorder
  • receptor-operated calcium entry
  • signal transduction
  • store-operated calcium entry
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