Targeting Potassium Channels Kv1.3 and KCa3.1: Routes to Selective Immunomodulators in Autoimmune Disorder Treatment?

The Kv1.3 and K(Ca)3.1 potassium channels are promising targets for the treatment of autoimmune disorders. Many Kv1.3 and K(Ca)3.1 blockers have a more favorable adverse event profiles than existing immunosuppressants, suggesting the selectivity of Kv1.3 and K(Ca)3.1 blockade. The Kv1.3 and K(Ca)3.1 blockers exert differential effects in different autoimmune diseases. The Kv1.3 inhibitors or gene deletion have been shown to have benefits in multiple sclerosis, type 1 diabetes, rheumatoid arthritis, psoriasis, and rapidly progressive glomerulonephritis. The K(Ca)3.1 blockers have demonstrated efficacy in human primary biliary cirrhosis and showed protective effects in animal models of severe colitis, allergic encephalomyelitis, inflammatory bowel disease, and multiple sclerosis. The K(Ca)3.1 blockers are not considered candidates for treatment of multiple sclerosis. The selective immunosuppressive effects of the Kv1.3 and K(Ca)3.1 blockers are due to the differences in their distribution on autoimmune-related immune cells and tissues and beta 1 integrin (very late activating antigen)-Kv1.3 channel cross-talk.