Ca2+-Activated K+ Channel KCa3.1 as a Therapeutic Target for Immune Disorders

In lymphoid and myeloid cells, membrane hyperpolarization by the opening of K+ channels increases the activity of Ca2+ release-activated Ca2+ (CRAC) channels and transient receptor potential (TRP) Ca2+ channels. The intermediate-conductance Ca2+-activated K+ channel K(Ca)3.1 plays an important role in cell proliferation, differentiation, migration, and cytokine production in innate and adaptive immune systems. K(Ca)3.1 is therefore an attractive therapeutic target for allergic, inflammatory, and autoimmune disorders. In the past several years, studies have provided new insights into 1) K(Ca)3.1 pharmacology and its auxiliary regulators; 2) post-transcriptional and proteasomal regulation of K(Ca)3.1; 3) K(Ca)3.1 as a regulator of immune cell migration, cytokine production, and phenotypic polarization; 4) the role of K(Ca)3.1 in the phosphorylation and nuclear translocation of Smad2/3; and 5) K(Ca)3.1 as a therapeutic target for cancer immunotherapy. In this review, we have assembled a comprehensive overview of current research on the physiological and patho-physiological significance of K(Ca)3.1 in the immune system.