| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Laboratoire d’Immunologie, Faculté de Médecine, Université de la Méditerranée;
Laboratoire de Neurobiologie des Canaux Ioniques, Unité de Formation et de Recherche de Médecine, Institut National de la Santé et de la Recherche Médicale Unité 464;
Laboratoire de Neurobiologie, Centre National de la Recherche Scientifique, Unité Propre de Recherche 9024;
Laboratoire d’Immunologie, Hôpital Sainte-Marguerite, Institut National de la Santé et de la Recherche Médicale Unité 387; and
¶ Laboratoire d’Ingénierie des Protéines, Institut Federatif de Recherche Jean Roche, Faculté de Médecine-Nord, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6560, Marseille, France
Kaliotoxin (KTX), a blocker of voltage-gated potassium channels (Kv), is highly selective for Kv1.1 and Kv1.3. First, Kv1.3 is expressed by T lymphocytes. Blockers of Kv1.3 inhibit T lymphocyte activation. Second, Kv1.1 is found in paranodal regions of axons in the central nervous system. Kv blockers improve the impaired neuronal conduction of demyelinated axons in vitro and potentiate the synaptic transmission. Therefore, we investigated the therapeutic properties of KTX via its immunosuppressive and symptomatic neurological effects, using experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. The T line cells used to induce adoptive EAE were myelin basic protein (MBP)-specific, constitutively contained mRNA for Kv1.3. and expressed Kv1.3. These channels were shown to be blocked by KTX. Activation is a crucial step for MBP T cells to become encephalitogenic. The addition of KTX during Ag-T cell activation led to a great reduction in the MBP T cell proliferative response, in the production of IL-2 and TNF, and in Ca2+ influx. Furthermore, the addition of KTX during T cell activation in vitro led a decreased encephalitogenicity of MBP T cells. Moreover, KTX injected into Lewis rats impaired T cell function such as the delayed-type hypersensitivity. Lastly, the administration of this blocker of neuronal and lymphocyte channels to Lewis rats improved the symptoms of EAE. We conclude that KTX is a potent immunosuppressive agent with beneficial effects on the neurological symptoms of EAE.
This article has been cited by other articles:
|
|
 |
|
  M. W. Pennington, C. Beeton, C. A. Galea, B. J. Smith, V. Chi, K. P. Monaghan, A. Garcia, S. Rangaraju, A. Giuffrida, D. Plank, et al. Engineering a Stable and Selective Peptide Blocker of the Kv1.3 Channel in T Lymphocytes Mol. Pharmacol., April 1, 2009; 75(4): 762 - 773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Han, H. Yi, S.-J. Yin, Z.-Y. Chen, H. Liu, Z.-J. Cao, Y.-L. Wu, and W.-X. Li Structural Basis of a Potent Peptide Inhibitor Designed for Kv1.3 Channel, a Therapeutic Target of Autoimmune Disease J. Biol. Chem., July 4, 2008; 283(27): 19058 - 19065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Meuth, S. Bittner, P. Meuth, O. J. Simon, T. Budde, and H. Wiendl TWIK-related Acid-sensitive K+ Channel 1 (TASK1) and TASK3 Critically Influence T Lymphocyte Effector Functions J. Biol. Chem., May 23, 2008; 283(21): 14559 - 14570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hu, M. Pennington, Q. Jiang, K. A. Whartenby, and P. A. Calabresi Characterization of the Functional Properties of the Voltage-Gated Potassium Channel Kv1.3 in Human CD4+ T Lymphocytes J. Immunol., October 1, 2007; 179(7): 4563 - 4570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Valujskikh and X. C. Li Frontiers in Nephrology: T Cell Memory as a Barrier to Transplant Tolerance J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2252 - 2261. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Herrero-Herranz, L. A. Pardo, G. Bunt, R. Gold, W. Stuhmer, and R. A. Linker Re-Expression of a Developmentally Restricted Potassium Channel in Autoimmune Demyelination: Kv1.4 Is Implicated in Oligodendroglial Proliferation Am. J. Pathol., August 1, 2007; 171(2): 589 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Nicolaou, P. Szigligeti, L. Neumeier, S. Molleran Lee, H. J. Duncan, S. K. Kant, A. B. Mongey, A. H. Filipovich, and L. Conforti Altered Dynamics of Kv1.3 Channel Compartmentalization in the Immunological Synapse in Systemic Lupus Erythematosus J. Immunol., July 1, 2007; 179(1): 346 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Beeton and K. G. Chandy Potassium Channels, Memory T Cells, and Multiple Sclerosis Neuroscientist, December 1, 2005; 11(6): 550 - 562. [Abstract] [PDF]
|
|
|
|
|
|
A. Schmitz, A. Sankaranarayanan, P. Azam, K. Schmidt-Lassen, D. Homerick, W. Hansel, and H. Wulff Design of PAP-1, a Selective Small Molecule Kv1.3 Blocker, for the Suppression of Effector Memory T Cells in Autoimmune Diseases Mol. Pharmacol., November 1, 2005; 68(5): 1254 - 1270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Rus, C. A. Pardo, L. Hu, E. Darrah, C. Cudrici, T. Niculescu, F. Niculescu, K. M. Mullen, R. Allie, L. Guo, et al. The voltage-gated potassium channel Kv1.3 is highly expressed on inflammatory infiltrates in multiple sclerosis brain PNAS, August 2, 2005; 102(31): 11094 - 11099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Valverde, T. Kawai, and M.A. Taubman Potassium Channel-blockers as Therapeutic Agents to Interfere with Bone Resorption of Periodontal Disease Journal of Dental Research, June 1, 2005; 84(6): 488 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Beeton, M. W. Pennington, H. Wulff, S. Singh, D. Nugent, G. Crossley, I. Khaytin, P. A. Calabresi, C.-Y. Chen, G. A. Gutman, et al. Targeting Effector Memory T Cells with a Selective Peptide Inhibitor of Kv1.3 Channels for Therapy of Autoimmune Diseases Mol. Pharmacol., April 1, 2005; 67(4): 1369 - 1381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Pardo Voltage-Gated Potassium Channels in Cell Proliferation Physiology, October 1, 2004; 19(5): 285 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wulff, H.-G. Knaus, M. Pennington, and K. G. Chandy K+ Channel Expression during B Cell Differentiation: Implications for Immunomodulation and Autoimmunity J. Immunol., July 15, 2004; 173(2): 776 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Khanna, E. J. Lee, and D. M. Papazian Transient calnexin interaction confers long-term stability on folded K+ channel protein in the ER J. Cell Sci., June 15, 2004; 117(14): 2897 - 2908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Vennekamp, H. Wulff, C. Beeton, P. A. Calabresi, S. Grissmer, W. Hansel, and K. G. Chandy Kv1.3-Blocking 5-Phenylalkoxypsoralens: A New Class of Immunomodulators Mol. Pharmacol., June 1, 2004; 65(6): 1364 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Beeton, H. Wulff, S. Singh, S. Botsko, G. Crossley, G. A. Gutman, M. D. Cahalan, M. Pennington, and K. G. Chandy A Novel Fluorescent Toxin to Detect and Investigate Kv1.3 Channel Up-regulation in Chronically Activated T Lymphocytes J. Biol. Chem., March 7, 2003; 278(11): 9928 - 9937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q.-H. Liu, B. K. Fleischmann, B. Hondowicz, C. C. Maier, L. A. Turka, K. Yui, M. I. Kotlikoff, A. D. Wells, and B. D. Freedman Modulation of Kv Channel Expression and Function by TCR and Costimulatory Signals during Peripheral CD4+ Lymphocyte Differentiation J. Exp. Med., October 7, 2002; 196(7): 897 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Colden-Stanfield Clustering of very late antigen-4 integrins modulates K+ currents to alter Ca2+-mediated monocyte function Am J Physiol Cell Physiol, September 1, 2002; 283(3): C990 - C1000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Beeton, H. Wulff, J. Barbaria, O. Clot-Faybesse, M. Pennington, D. Bernard, M. D. Cahalan, K. G. Chandy, and E. Beraud Selective blockade of T lymphocyte K+ channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis PNAS, November 20, 2001; 98(24): 13942 - 13947. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
