Inhibition of the K+ channel KCa3.1 ameliorates T cell-mediated colitis

Lie Di, Shekhar Srivastava, Olga Zhdanova, Yi Ding, Zhai Li, Heike Wulff, Maria Lafaille, Edward Y. Skolnik

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118 Scopus citations


The calcium-activated K+ channel KCa3.1 plays an important role in T lymphocyte Ca2+ signaling by helping to maintain a negative membrane potential, which provides an electrochemical gradient to drive Ca 2+ influx. To assess the role of KCa3.1 channels in lymphocyte activation in vivo, we studied T cell function in KCa3.1-/- mice. CD4 T helper (i.e., Th0) cells isolated from KCa3.1-/- mice lacked KCa3.1 channel activity, which resulted in decreased T cell receptor-stimulated Ca2+ influx and IL-2 production. Although loss of KCa3.1 did not interfere with CD4 T cell differentiation, both Ca2+ influx and cytokine production were impaired in KCa3.1-/- Th1 and Th2 CD4 T cells, whereas T regulatory and Th17 function were normal. We found that inhibition of KCa3.1-/- protected mice from developing severe colitis in two mouse models of inflammatory bowel disease, which were induced by (i) the adoptive transfer of mouse naïve CD4T cells into rag2-/- recipients and (ii) trinitrobenzene sulfonic acid. Pharmacologic inhibitors of KCa3.1 have already been shown to be safe in humans. Thus, if these preclinical studies continue to show efficacy, it may be possible to rapidly test whether KCa3.1 inhibitors are efficacious in patients with inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.

Original languageEnglish
Pages (from-to)1541-1546
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
StatePublished - 26 Jan 2010
Externally publishedYes


  • Calcium signaling
  • Inflammatory bowel disease
  • Potassium channels
  • T helper cells
  • T-cell signaling


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