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Ca2+ waves initiate antigen-stimulated Ca2+ responses in mast cells

Roy Cohen1, Alexis Torres, Hong-Tao Ma

  • 1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14850, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|October 30, 2009
PubMed

Insights

Calcium (Ca2+) waves in mast cells originate from cell protrusions, driven by TRPC channels. This spatial signaling is crucial for cellular responses following immunoreceptor activation.

Area of Science:

  • Cellular Biology
  • Immunology
  • Biophysics

Background:

  • Calcium (Ca2+) mobilization is fundamental to mast cell functions like exocytosis and cytokine release.
  • Understanding the spatial dynamics of Ca2+ signaling is key to deciphering cellular activation pathways.

Purpose of the Study:

  • To investigate the spatial origins and characteristics of Ca2+ waves in mast cells upon stimulation.
  • To identify the molecular mechanisms, particularly ion channels, involved in initiating and regulating these Ca2+ responses.

Main Methods:

  • Single-cell stimulation using IgE-specific antigen (Ag) and high-speed imaging of Ca2+ sensors.
  • Utilizing rat basophilic leukemia and bone marrow-derived rat mast cells.
  • Employing RNA interference (RNAi) to knock down transient receptor potential channel (TRPC)1 and TRPC3.

Main Results:

  • Ca2+ waves predominantly initiated at the tips of cell protrusions, followed by oscillations.
  • Localized Ca2+ puffs occurred at the cell contact site when stimulated with a micropipette-bound Ag.
  • TRPC1 and TRPC3 channel knockdown altered Ag sensitivity and shifted Ca2+ wave initiation to the cell body.

Conclusions:

  • Ca2+ signaling in mast cells exhibits spatial encoding, with wave initiation sites specified by TRPC channels.
  • TRPC channels play a critical role in regulating the location and propagation of Ca2+ signals following immunoreceptor activation.

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