Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4

Nat Immunol. 2007 Mar;8(3):312-20. doi: 10.1038/ni1441. Epub 2007 Feb 11.


Mast cells are key effector cells in allergic reactions. Aggregation of the receptor FcepsilonRI in mast cells triggers the influx of calcium (Ca(2+)) and the release of inflammatory mediators. Here we show that transient receptor potential TRPM4 proteins acted as calcium-activated nonselective cation channels and critically determined the driving force for Ca(2+) influx in mast cells. Trpm4(-/-) bone marrow-derived mast cells had more Ca(2+) entry than did TRPM4(+/+) cells after FcepsilonRI stimulation. Consequently, Trpm4(-/-) bone marrow-derived mast cells had augmented degranulation and released more histamine, leukotrienes and tumor necrosis factor. Trpm4(-/-) mice had a more severe IgE-mediated acute passive cutaneous anaphylactic response, whereas late-phase passive cutaneous anaphylaxis was not affected. Our results establish the physiological function of TRPM4 channels as critical regulators of Ca(2+) entry in mast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphylaxis / immunology*
  • Anaphylaxis / metabolism
  • Animals
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Calcium / metabolism
  • Immunoglobulin E / immunology*
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Membrane Potentials
  • Mice
  • Patch-Clamp Techniques
  • Receptors, IgE / immunology
  • Receptors, IgE / metabolism
  • TRPM Cation Channels / metabolism*


  • Receptors, IgE
  • TRPM Cation Channels
  • TRPM4 protein, mouse
  • Immunoglobulin E
  • Calcium