Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 145K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liu, Q.-H. Articles by Freedman, B. D. Search for Related Content PubMed PubMed Citation Articles by Liu, Q.-H. Articles by Freedman, B. D. Social Bookmarking                            What's this?

Modulation of Kv Channel Expression and Function by TCR and Costimulatory Signals during Peripheral CD4⁺ Lymphocyte Differentiation

Qing-Hua Liu¹, Bernd K. Fleischmann², Brian Hondowicz¹, Curtis C. Maier³, Laurence A. Turka⁴, Katsuyuki Yui⁶, Michael I. Kotlikoff⁵, Andrew D. Wells⁴ and Bruce D. Freedman¹

¹ Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
² Institute für Neurophysiologie, University of Cologne, Cologne D-50931, Germany
³ Department of Safety Assessment, GlaxoSmithKline, King of Prussia, PA 19406
⁴ Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
⁵ Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
⁶ Department of Immunology, Nagasaki University, School of Medicine, Nagasaki, 852-8523, Japan

Address correspondence to Bruce D. Freedman, Dept. of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104. Phone: 215-573-8218; Fax: 215-898-0719; E-mail: bruce{at}vet.upenn.edu

Ionic signaling pathways, including voltage-dependent potassium (Kv) channels, are instrumental in antigen-mediated responses of peripheral T cells. However, how Kv channels cooperate with other signaling pathways involved in T cell activation and differentiation is unknown. We report that multiple Kv channels are expressed by naive CD4⁺ lymphocytes, and that the current amplitude and kinetics are modulated by antigen receptor–mediated stimulation and costimulatory signals. Currents expressed in naive CD4⁺ lymphocytes are consistent with Kv1.1, Kv1.2, Kv1.3, and Kv1.6. Effector CD4⁺ cells generated by optimal TCR and costimulation exhibit only Kv1.3 current, but at approximately sixfold higher levels than naive cells. CD4⁺ lymphocytes anergized through partial stimulation exhibit similar Kv1.1, Kv1.2, and/or Kv1.6 currents, but approximately threefold more Kv1.3 current than naive cells. To determine if Kv channels contribute to the distinct functions of naive, effector, and anergized T cells, we tested their role in immunoregulatory cytokine production. Each Kv channel is required for maximal IL-2 production by naive CD4⁺ lymphocytes, whereas none appears to play a role in IL-2, IL-4, or IFN- production by effector cells. Interestingly, Kv channels in anergized lymphocytes actively suppress IL-4 production, and these functions are consistent with a role in regulating the membrane potential and calcium signaling.

Key Words: potassium channel • CD28 • patch clamp • superantigen • anergy

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Sole, L., Roura-Ferrer, M., Perez-Verdaguer, M., Oliveras, A., Calvo, M., Fernandez-Fernandez, J. M., Felipe, A. (2009). KCNE4 suppresses Kv1.3 currents by modulating trafficking, surface expression and channel gating. J. Cell Sci. 122: 3738-3748 [Abstract] [Full Text]  
• Nolz, J. C., Medeiros, R. B., Mitchell, J. S., Zhu, P., Freedman, B. D., Shimizu, Y., Billadeau, D. D. (2007). WAVE2 Regulates High-Affinity Integrin Binding by Recruiting Vinculin and Talin to the Immunological Synapse. Mol. Cell. Biol. 27: 5986-6000 [Abstract] [Full Text]  
• Liu, X., Zhu, P., Freedman, B. D. (2006). Multiple eicosanoid-activated nonselective cation channels regulate B-lymphocyte adhesion to integrin ligands. Am. J. Physiol. Cell Physiol. 290: C873-C882 [Abstract] [Full Text]  
• Eck, S. C., Zhu, P., Pepper, M., Bensinger, S. J., Freedman, B. D., Laufer, T. M. (2006). Developmental Alterations in Thymocyte Sensitivity Are Actively Regulated by MHC Class II Expression in the Thymic Medulla. J. Immunol. 176: 2229-2237 [Abstract] [Full Text]  
• Beeton, C., Chandy, K. G. (2005). Potassium Channels, Memory T Cells, and Multiple Sclerosis. Neuroscientist 11: 550-562 [Abstract]  
• Liu, Q.-H., Liu, X., Wen, Z., Hondowicz, B., King, L., Monroe, J., Freedman, B. D. (2005). Distinct Calcium Channels Regulate Responses of Primary B Lymphocytes to B Cell Receptor Engagement and Mechanical Stimuli. J. Immunol. 174: 68-79 [Abstract] [Full Text]  
• Wulff, H., Knaus, H.-G., Pennington, M., Chandy, K. G. (2004). K+ Channel Expression during B Cell Differentiation: Implications for Immunomodulation and Autoimmunity. J. Immunol. 173: 776-786 [Abstract] [Full Text]  
• Nam, J. H., Woo, J.-E., Uhm, D.-Y., Kim, S. J. (2004). Membrane-delimited Regulation of Novel Background K+ Channels by MgATP in Murine Immature B Cells. J. Biol. Chem. 279: 20643-20654 [Abstract] [Full Text]  
• Xu, J., Wang, P., Li, Y., Li, G., Kaczmarek, L. K., Wu, Y., Koni, P. A., Flavell, R. A., Desir, G. V. (2004). The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity. Proc. Natl. Acad. Sci. USA 101: 3112-3117 [Abstract] [Full Text]  
• Xu, J., Koni, P. A., Wang, P., Li, G., Kaczmarek, L., Wu, Y., Li, Y., Flavell, R. A., Desir, G. V. (2003). The voltage-gated potassium channel Kv1.3 regulates energy homeostasis and body weight. Hum Mol Genet 12: 551-559 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS