K+ channels as targets for specific immunomodulation.
The voltage-gated Kv1.3 channel and the Ca(2+)-activated IKCa1 K(+) channel are expressed in T cells in a distinct pattern that depends on the state of lymphocyte activation and differentiation. The channel phenotype changes during the progression from the resting to the activated cell state and from naïve to effector memory cells, affording promise for specific immunomodulatory actions of K(+) channel blockers. In this article, we review the functional roles of these channels in both naïve cells and memory cells, describe the development of selective inhibitors of Kv1.3 and IKCa1 channels, and provide a rationale for the potential therapeutic use of these inhibitors in immunological disorders.
Chandy
K George
KG
Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA. gchandy@uci.edu
Wulff
Heike
H
Beeton
Christine
C
Pennington
Michael
M
Gutman
George A
GA
Cahalan
Michael D
MD
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels