The K+ channel iKCA1 potentiates Ca2+ influx and degranulation in human lung mast cells

J Allergy Clin Immunol. 2004 Jul;114(1):66-72. doi: 10.1016/j.jaci.2004.04.005.


Background: Human lung and blood-derived mast cells express a Ca2+-activated K+ channel (KCA) that has electrophysiological properties resembling the intermediate conductance KCA (iKCA1). This channel is predicted to enhance IgE-dependent mast cell responses.

Objective: To confirm the identity of this channel as iKCA1 in human lung mast cells and to examine the effect of an iKCA1 opener, 1-ethyl-2-benzimidazolinone (1-EBIO), on Ca2+ influx and degranulation after IgE-dependent activation.

Methods: iKCA1 expression was examined by using RT-PCR. Ion currents were measured by using the patch clamp technique in human peripheral blood-derived mast cells, freshly isolated human lung mast cells (HLMCs), and long-term cultured HLMCs (LTHLMCs). Currents were manipulated with the specific iKCA1 opener 1-EBIO and the iKCA1 blockers clotrimazole and TRAM-34. Ratiometric Ca2+ imaging was performed on single fura-2-loaded cells, and histamine release was measured by radioenzymatic assay.

Results: Both fresh HLMCs and LTHLMCs expressed iKCA1 mRNA. The iKCA1 opener 1-EBIO induced iKCA1 currents in 89% of human peripheral blood-derived mast cells, 12% of fresh HLMCs, and 67% of LTHLMCs, which were blocked by the iKCA1 blockers clotrimazole and TRAM-34. After cell activation with a suboptimal concentration of anti-IgE, 1-EBIO enhanced the IgE-dependent rise in cytosolic-free Ca2+ and potentiated IgE-dependent histamine release.

Conclusion: Opening of iKCA1 enhances IgE-dependent Ca2+ influx and histamine release in HLMCs. Inhibition of iKCA1 may provide a novel approach to the treatment of mast cell-mediated disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / pharmacology
  • Calcium / metabolism*
  • Calcium Channel Agonists / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Cell Degranulation / drug effects
  • Cell Degranulation / immunology*
  • Cells, Cultured
  • Clotrimazole / pharmacology
  • Histamine / immunology
  • Humans
  • Immunoglobulin E / immunology
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Lung / cytology
  • Lung / immunology
  • Mast Cells / drug effects
  • Mast Cells / immunology*
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Pyrazoles / pharmacology


  • Benzimidazoles
  • Calcium Channel Agonists
  • Calcium Channel Blockers
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • KCNN4 protein, human
  • Potassium Channels
  • Pyrazoles
  • TRAM 34
  • Immunoglobulin E
  • Histamine
  • Clotrimazole
  • 1-ethyl-2-benzimidazolinone
  • Calcium