Chronic lithium treatment attenuates intracellular calcium mobilization

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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.

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

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