Ion channels in NK cells: Signaling and functions

Ion channels are integral membrane proteins that facilitate rapid transport of small ions into and out of the cell and between organelles and cytosol. Cytolytic lymphocytes including natural killer (NK) cells principally kill virus-infected and cancer cells by releasing cytolytic granules within the immunological synapse, formed between target and effector cells. This process strongly depends on Ca2+ signaling, which in human NK cells is controlled by the PLCγ/IP3R/CRAC axis. It is believed that CRAC, a Ca2+-selective channel within the cell membrane, is a principal mediator of Ca+ entry in nonexcitable cells including immune cells. However, in addition to CRAC, the activity of other plasma membrane and organellar channels, which are permeable for Ca2+ and Na+, K+, or small anions, also plays important roles in regulating NK cell functions. In this review, we discuss the role of different ion channels in the NK-mediated immune response including members of 4 distinct families of K+-selective channels, transient receptor potential channels, purinergic receptors, and pentameric ligand-gated channels that are located in the plasma membrane and lysosomes of NK cells.