Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels

Christopher M. Fanger, Heiko Rauer, Amber L. Neben, Mark J. Miller, Heike Rauer, Heike Wulff, Joaquin Campos Rosa, C. Robin Ganellin, K. George Chandy, Michael D. Cahalan

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

To maintain Ca2+ entry during T lymphocyte activation, a balancing efflux of cations is necessary. Using three approaches, we demonstrate that this cation efflux is mediated by Ca2+-activated K+ (KCa) channels, hSKCa2 in the human leukemic T cell line Jurkat and hIKCa1 in mitogen-activated human T cells. First, several recently developed, selective and potent pharmacological inhibitors of K Ca channels but not KV channels reduce Ca2+ entry in Jurkat and in mitogen-activated human T cells. Second, dominant-negative suppression of the native KCa channel in Jurkat T cells by overexpression of a truncated fragment of the cloned hSKCa2 channel decreases Ca2+ influx. Finally, introduction of the hIKCa1 channel into Jurkat T cells maintains rapid Ca2+ entry despite pharmacological inhibition of the native small conductance KCa channel. Thus, KCa channels play a vital role in T cell Ca 2+ signaling.

Original languageEnglish (US)
Pages (from-to)12249-12256
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number15
DOIs
StatePublished - Apr 13 2001

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Calcium-Activated Potassium Channels
Calcium Signaling
T-cells
Calcium
T-Lymphocytes
Jurkat Cells
Mitogens
Cations
Pharmacology
Lymphocyte Activation
Chemical activation
Cell Line

ASJC Scopus subject areas

  • Biochemistry

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Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels. / Fanger, Christopher M.; Rauer, Heiko; Neben, Amber L.; Miller, Mark J.; Rauer, Heike; Wulff, Heike; Rosa, Joaquin Campos; Ganellin, C. Robin; Chandy, K. George; Cahalan, Michael D.

In: Journal of Biological Chemistry, Vol. 276, No. 15, 13.04.2001, p. 12249-12256.

Research output: Contribution to journalArticle

Fanger, CM, Rauer, H, Neben, AL, Miller, MJ, Rauer, H, Wulff, H, Rosa, JC, Ganellin, CR, Chandy, KG & Cahalan, MD 2001, 'Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels', Journal of Biological Chemistry, vol. 276, no. 15, pp. 12249-12256. https://doi.org/10.1074/jbc.M011342200
Fanger, Christopher M. ; Rauer, Heiko ; Neben, Amber L. ; Miller, Mark J. ; Rauer, Heike ; Wulff, Heike ; Rosa, Joaquin Campos ; Ganellin, C. Robin ; Chandy, K. George ; Cahalan, Michael D. / Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 15. pp. 12249-12256.
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AU - Neben, Amber L.

AU - Miller, Mark J.

AU - Rauer, Heike

AU - Wulff, Heike

AU - Rosa, Joaquin Campos

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AU - Cahalan, Michael D.

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AB - To maintain Ca2+ entry during T lymphocyte activation, a balancing efflux of cations is necessary. Using three approaches, we demonstrate that this cation efflux is mediated by Ca2+-activated K+ (KCa) channels, hSKCa2 in the human leukemic T cell line Jurkat and hIKCa1 in mitogen-activated human T cells. First, several recently developed, selective and potent pharmacological inhibitors of K Ca channels but not KV channels reduce Ca2+ entry in Jurkat and in mitogen-activated human T cells. Second, dominant-negative suppression of the native KCa channel in Jurkat T cells by overexpression of a truncated fragment of the cloned hSKCa2 channel decreases Ca2+ influx. Finally, introduction of the hIKCa1 channel into Jurkat T cells maintains rapid Ca2+ entry despite pharmacological inhibition of the native small conductance KCa channel. Thus, KCa channels play a vital role in T cell Ca 2+ signaling.

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