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Targeting Potassium Channels K v1.3 and K C a 3.1: Routes to Selective Immunomodulators in Autoimmune Disorder Treatment?
Author(s) -
Wang Jun,
Xiang Ming
Publication year - 2013
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1236
Subject(s) - experimental autoimmune encephalomyelitis , multiple sclerosis , rheumatoid arthritis , autoimmune disease , primary biliary cirrhosis , immunology , psoriasis , medicine , inflammatory bowel disease , immune system , adverse effect , pharmacology , chemistry , antibody , disease
The Kv1.3 and K C a 3.1 potassium channels are promising targets for the treatment of autoimmune disorders. Many K v1.3 and K C a 3.1 blockers have a more favorable adverse event profiles than existing immunosuppressants, suggesting the selectivity of K v1.3 and K C a 3.1 blockade. The K v1.3 and K C a 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 C a 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 C a 3.1 blockers are not considered candidates for treatment of multiple sclerosis. The selective immunosuppressive effects of the Kv1.3 and K C a 3.1 blockers are due to the differences in their distribution on autoimmune–related immune cells and tissues and β1 integrin (very late activating antigen)– K v1.3 channel cross‐talk.