1. ¹Laboratory of Cellular and Molecular Pathophysiology, Center for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
2. ²Departments of Biochemistry, University of Toronto, Toronto, Ontario, Canada
3. ³Departments of Pharmacology, University of Toronto, Toronto, Ontario, Canada
4. ⁴Departments of Psychiatry, University of Toronto, Toronto, Ontario, Canada
5. ⁵Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

Correspondence: Dr JJ Warsh, Laboratory of Cellular and Molecular Pathophysiology, Center for Addiction and Mental Health-Clarke Site, 250 College Street, Toronto, Ontario, Canada M5T 1R8. Tel: +1 416 979 4279; Fax: +1 416 979 4730; E-mail: jerry_warsh@camh.net

Received 4 March 2004; Revised 11 May 2004; Accepted 17 June 2004; Published online 31 August 2004.

Abstract

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 (Ca²⁺) responses. As these findings suggest that chronic lithium treatment modifies receptor (ROCE) and/or store-operated Ca²⁺ 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 Ca²⁺ disturbances as observed in BD.