Chronic lithium treatment attenuates intracellular calcium mobilization

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

Research output: Contribution to journalArticle

62 Citations (Scopus)

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 2004
Externally publishedYes

Fingerprint

Lithium
Calcium
Cell Line
Bipolar Disorder
Homeostasis
Therapeutics
Healthy Volunteers
Fluorometry
Thapsigargin
Fura-2
Signal Transduction
Proteins

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Wasserman, M. J., Corson, T., 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

Chronic lithium treatment attenuates intracellular calcium mobilization. / Wasserman, Michael J.; Corson, Timothy; Sibony, David; Cooke, Robert G.; Parikh, Sagar V.; Pennefather, Peter S.; Li, Peter P.; Warsh, Jerry J.

In: Neuropsychopharmacology, Vol. 29, No. 4, 04.2004, p. 759-769.

Research output: Contribution to journalArticle

Wasserman, MJ, Corson, T, Sibony, D, Cooke, RG, Parikh, SV, Pennefather, PS, Li, PP & Warsh, JJ 2004, 'Chronic lithium treatment attenuates intracellular calcium mobilization', Neuropsychopharmacology, vol. 29, no. 4, pp. 759-769. https://doi.org/10.1038/sj.npp.1300400
Wasserman MJ, Corson T, Sibony D, Cooke RG, Parikh SV, Pennefather PS et al. Chronic lithium treatment attenuates intracellular calcium mobilization. Neuropsychopharmacology. 2004 Apr;29(4):759-769. https://doi.org/10.1038/sj.npp.1300400
Wasserman, Michael J. ; Corson, Timothy ; Sibony, David ; Cooke, Robert G. ; Parikh, Sagar V. ; Pennefather, Peter S. ; Li, Peter P. ; Warsh, Jerry J. / Chronic lithium treatment attenuates intracellular calcium mobilization. In: Neuropsychopharmacology. 2004 ; Vol. 29, No. 4. pp. 759-769.
@article{335b8bd5599b45eab33bc6170578b094,
title = "Chronic lithium treatment attenuates intracellular calcium mobilization",
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.",
keywords = "B lymphoblast, Bipolar disorder, Intracellular calcium mobilization, Lithium, Pathophysiology, Signal transduction",
author = "Wasserman, {Michael J.} and Timothy Corson and David Sibony and Cooke, {Robert G.} and Parikh, {Sagar V.} and Pennefather, {Peter S.} and Li, {Peter P.} and Warsh, {Jerry J.}",
year = "2004",
month = "4",
doi = "10.1038/sj.npp.1300400",
language = "English (US)",
volume = "29",
pages = "759--769",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Chronic lithium treatment attenuates intracellular calcium mobilization

AU - Wasserman, Michael J.

AU - Corson, Timothy

AU - Sibony, David

AU - Cooke, Robert G.

AU - Parikh, Sagar V.

AU - Pennefather, Peter S.

AU - Li, Peter P.

AU - Warsh, Jerry J.

PY - 2004/4

Y1 - 2004/4

N2 - 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.

AB - 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.

KW - B lymphoblast

KW - Bipolar disorder

KW - Intracellular calcium mobilization

KW - Lithium

KW - Pathophysiology

KW - Signal transduction

UR - http://www.scopus.com/inward/record.url?scp=1642447682&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642447682&partnerID=8YFLogxK

U2 - 10.1038/sj.npp.1300400

DO - 10.1038/sj.npp.1300400

M3 - Article

VL - 29

SP - 759

EP - 769

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 4

ER -