Kv1.3 potassium channels as a therapeutic target in multiple sclerosis.
We discuss the potential use of inhibitors of Kv1.3 potassium channels in T lymphocytes as therapeutics for multiple sclerosis. Current treatment strategies target the immune system in a non-selective manner. The resulting general immunosuppression, toxic side-effects and increased risk of opportunistic infections create the need for more selective therapeutics. Autoreactive effector-memory T (T(EM)) cells, considered to be major mediators of autoimmunity, express large numbers of Kv1.3 channels. Selective blockers of Kv1.3 inhibit calcium signaling, cytokine production and proliferation of T(EM) cells in vitro, and T(EM) cell-motility in vivo. Kv1.3 blockers ameliorate disease in animal models of multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus and contact dermatitis without compromising the protective immune response to acute infections. Kv1.3 blockers have a good safety profile in rodents and primates.
Rangaraju
Srikant
S
University of California, Department of Physiology and Biophysics, Irvine, California 92697, USA.
Chi
Victor
V
Pennington
Michael W
MW
Chandy
K George
KG
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D026902:Potassium Channel Blockers / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers