Chronic lithium treatment attenuates intracellular calcium mobilization

Neuropsychopharmacology. 2004 Apr;29(4):759-69. doi: 10.1038/sj.npp.1300400.


Elevated basal intracellular calcium (Ca(2+)) levels ([Ca(2+)](B)) in B lymphoblast cell lines (BLCLs) from bipolar I disorder (BD-I) patients implicate altered Ca(2+) homeostasis in this illness. Chronic lithium treatment affects key proteins modulating intracellular Ca(2+) signaling. Thus, we sought to determine if chronic exposure to therapeutic lithium concentrations also modifies intracellular Ca(2+) homeostasis in this surrogate cellular model of signal transduction disturbances in BD. BLCLs from BD-I (N=26) and healthy subjects (N=17) were regrown from frozen stock and incubated with 0.75 mM lithium or vehicle for 24 h (acute) or 7 days (chronic). [Ca(2+)](B), lysophosphatidic acid (LPA)-stimulated Ca(2+) mobilization ([Ca(2+)](S)), and thapsigargin-induced store-operated Ca(2+) entry (SOCE) were determined using ratiometric fluorometry with Fura-2. Compared with vehicle, chronic lithium exposure resulted in significantly higher [Ca(2+)](B) (F=8.47; p=0.006) in BLCLs from BD-I and healthy subjects. However, peak LPA-stimulated [Ca(2+)](S) and SOCE were significantly reduced (F=11.1, p=0.002 and F=8.36, p=0.007, respectively). Acute lithium exposure did not significantly affect measured parameters. In summary, the effect of chronic lithium to elevate [Ca(2+)](B) in BLCLs while attenuating both receptor-stimulated and SOCE components of intracellular Ca(2+) mobilization in BLCLs suggests that modulation of intracellular Ca(2+) homeostasis may be important to the therapeutic action of lithium.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / virology
  • Bipolar Disorder / drug therapy
  • Calcium / metabolism*
  • Case-Control Studies
  • Cell Count
  • Cell Line
  • Cell Transformation, Viral / drug effects
  • Chi-Square Distribution
  • Drug Administration Schedule
  • Enzyme Inhibitors / pharmacology
  • Female
  • Fura-2 / metabolism
  • Herpesvirus 4, Human / metabolism
  • Homeostasis / drug effects*
  • Humans
  • Intracellular Space / drug effects*
  • Intracellular Space / metabolism
  • Lithium / pharmacology*
  • Lithium / therapeutic use
  • Lysophospholipids / pharmacology
  • Male
  • Multivariate Analysis
  • Thapsigargin / pharmacology
  • Time Factors


  • Enzyme Inhibitors
  • Lysophospholipids
  • Thapsigargin
  • Lithium
  • lysophosphatidic acid
  • Calcium
  • Fura-2