K+ channels as targets for specific immunomodulation

被引:375
作者
Chandy, KG [1 ]
Wulff, H
Beeton, C
Pennington, M
Gutman, GA
Cahalan, MD
机构
[1] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA
[2] Univ Calif Davis, Dept Pharmacol & Toxicol, Davis, CA 95616 USA
[3] Bachem Biosci, King Of Prussia, PA 19406 USA
关键词
D O I
10.1016/j.tips.2004.03.010
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The voltage-gated Kv1.3 channel and the Ca2+-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 naive 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 naive 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.
引用
收藏
页码:280 / 289
页数:10
相关论文
共 87 条
[1]   ION CHANNELS AND B-CELL MITOGENESIS [J].
AMIGORENA, S ;
CHOQUET, D ;
TEILLAUD, JL ;
KORN, H ;
FRIDMAN, WH .
MOLECULAR IMMUNOLOGY, 1990, 27 (12) :1259-1268
[2]   A novel fluorescent toxin to detect and investigate Kv1.3 channel up-regulation in chronically activated T lymphocytes [J].
Beeton, C ;
Wulff, H ;
Singh, S ;
Botsko, S ;
Crossley, G ;
Gutman, GA ;
Cahalan, MD ;
Pennington, M ;
Chandy, KG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (11) :9928-9937
[3]   Selective blockade of T lymphocyte K+ channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis [J].
Beeton, C ;
Wulff, H ;
Barbaria, J ;
Clot-Faybesse, O ;
Pennington, M ;
Bernard, D ;
Cahalan, MD ;
Chandy, KG ;
Béraud, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13942-13947
[4]  
Blanc E, 1997, PROTEINS, V29, P321, DOI 10.1002/(SICI)1097-0134(199711)29:3&lt
[5]  
321::AID-PROT6&gt
[6]  
3.0.CO
[7]  
2-D
[8]   Molecular properties and physiological roles of ion channels in the immune system [J].
Cahalan, MD ;
Wulff, H ;
Chandy, KG .
JOURNAL OF CLINICAL IMMUNOLOGY, 2001, 21 (04) :235-252
[9]   Maurotoxin:: A potent inhibitor of intermediate conductance Ca2+-activated potassium channels [J].
Castle, NA ;
London, DO ;
Creech, C ;
Fajloun, Z ;
Stocker, JW ;
Sabatier, JM .
MOLECULAR PHARMACOLOGY, 2003, 63 (02) :409-418
[10]   Suppression of the rat microglia Kv1.3 current by src-family tyrosine kinases and oxygen/glucose deprivation [J].
Cayabyab, FS ;
Khanna, R ;
Jones, OT ;
Schlichter, LC .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (06) :1949-1960