Chronic lithium treatment attenuates intracellular calcium mobilization

Michael J. Wasserman, Timothy W. Corson, David Sibony, Robert G. Cooke, Sagar V. Parikh, Peter S. Pennefather, Peter P. Li, Jerry J. Warsh

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Elevated basal intracellular calcium (Ca2+) levels ([Ca 2+]B) in B lymphoblast cell lines (BLCLs) from bipolar I disorder (BD-I) patients implicate altered Ca2+ homeostasis in this illness. Chronic lithium treatment affects key proteins modulating intracellular Ca2+ signaling. Thus, we sought to determine if chronic exposure to therapeutic lithium concentrations also modifies intracellular Ca2+ 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). [Ca2+] B, lysophosphatidic acid (LPA)-stimulated Ca2+ mobilization ([Ca2+]S), and thapsigargin-induced store-operated Ca2+ entry (SOCE) were determined using ratiometric fluorometry with Fura-2. Compared with vehicle, chronic lithium exposure resulted in significantly higher [Ca2+]B (F = 8.47; p = 0.006) in BLCLs from BD-I and healthy subjects. However, peak LPA-stimulated [Ca2+]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 [Ca2+]B in BLCLs while attenuating both receptor-stimulated and SOCE components of intracellular Ca2+ mobilization in BLCLs suggests that modulation of intracellular Ca2+ homeostasis may be important to the therapeutic action of lithium.

Original languageEnglish (US)
Pages (from-to)759-769
Number of pages11
JournalNeuropsychopharmacology
Volume29
Issue number4
DOIs
StatePublished - Apr 1 2004
Externally publishedYes

Keywords

  • B lymphoblast
  • Bipolar disorder
  • Intracellular calcium mobilization
  • Lithium
  • Pathophysiology
  • Signal transduction

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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  • Cite this

    Wasserman, M. J., Corson, T. W., Sibony, D., Cooke, R. G., Parikh, S. V., Pennefather, P. S., Li, P. P., & Warsh, J. J. (2004). Chronic lithium treatment attenuates intracellular calcium mobilization. Neuropsychopharmacology, 29(4), 759-769. https://doi.org/10.1038/sj.npp.1300400