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Ion channels in NK cells: Signaling and functions

Igor Pottosin1, Kathya Villatoro-Gómez1, Miguel Olivas-Aguirre2,3

  • 1Laboratory of Immunobiology and Ionic Transport Regulation, Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Avenida 25 de Julio 965, Villa de San Sebastián, Colima 28045, Mexico.

Journal of Leukocyte Biology
|September 10, 2025
PubMed

Insights

Ion channels are crucial for natural killer (NK) cell function in immunity. This review explores various ion channels, beyond CRAC, that regulate NK cell responses and immune signaling.

Area of Science:

  • Immunology
  • Cell Biology
  • Biophysics

Background:

  • Ion channels are essential membrane proteins for cellular ion transport.
  • Natural killer (NK) cells use cytolytic granules to eliminate virus-infected and cancer cells via the immunological synapse.
  • Calcium (Ca2+) signaling, regulated by the PLCγ/IP3R/CRAC axis, is critical for NK cell cytotoxicity.

Purpose of the Study:

  • To review the diverse roles of ion channels in NK cell-mediated immune responses.
  • To highlight the importance of various ion channels beyond the CRAC channel in NK cell function.
  • To discuss ion channels located in the plasma membrane and lysosomes of NK cells.

Main Methods:

  • Literature review of scientific articles on ion channels and NK cell function.
  • Analysis of the roles of different ion channel families in immune cell signaling.
  • Examination of ion channel localization within NK cells (plasma membrane, lysosomes).

Main Results:

  • CRAC channels are key for Ca2+ entry in nonexcitable cells like immune cells.
  • Other plasma membrane and organellar channels permeable to Ca2+, Na+, K+, and anions also significantly regulate NK cell functions.
  • Four distinct families of K+-selective channels, TRP channels, purinergic receptors, and pentameric ligand-gated channels are involved.

Conclusions:

  • NK cell-mediated immunity relies on a complex network of ion channels, not solely CRAC channels.
  • Understanding these diverse ion channels provides insights into NK cell regulation and potential therapeutic targets.
  • Further research into these channels can advance our knowledge of immune responses and cancer/viral infections.
Keywords:
Ca2+ signalingNK cellcancerion channellysosome

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