Differential calcium signaling and Kv1.3 trafficking to the immunological synapse in systemic lupus erythematosus

Cell Calcium. 2010 Jan;47(1):19-28. doi: 10.1016/j.ceca.2009.11.001. Epub 2009 Dec 2.


Systemic lupus erythematosus (SLE) T cells exhibit several activation signaling anomalies including defective Ca(2+) response and increased NF-AT nuclear translocation. The duration of the Ca(2+) signal is critical in the activation of specific transcription factors and a sustained Ca(2+) response activates NF-AT. Yet, the distribution of Ca(2+) responses in SLE T cells is not known. Furthermore, the mechanisms responsible for Ca(2+) alterations are not fully understood. Kv1.3 channels control Ca(2+) homeostasis in T cells. We reported a defect in Kv1.3 trafficking to the immunological synapse (IS) of SLE T cells that might contribute to the Ca(2+) defect. The present study compares single T cell quantitative Ca(2+) responses upon formation of the IS in SLE, normal, and rheumatoid arthritis (RA) donors. Also, we correlated cytosolic Ca(2+) concentrations and Kv1.3 trafficking in the IS by two-photon microscopy. We found that sustained [Ca(2+)](i) elevations constitute the predominant response to antigen stimulation of SLE T cells. This defect is selective to SLE as it was not observed in RA T cells. Further, we observed that in normal T cells termination of Ca(2+) influx is accompanied by Kv1.3 permanence in the IS, while Kv1.3 premature exit from the IS correlates with sustained Ca(2+) responses in SLE T cells. Thus, we propose that Kv1.3 trafficking abnormalities contribute to the altered distribution in Ca(2+) signaling in SLE T cells. Overall these defects may explain in part the T cell hyperactivity and dysfunction documented in SLE patients.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Calcium Signaling / drug effects
  • Calcium Signaling / immunology*
  • Cell Line, Transformed
  • Female
  • Humans
  • Immunological Synapses / immunology
  • Kv1.3 Potassium Channel / immunology
  • Kv1.3 Potassium Channel / metabolism*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / physiology
  • Male
  • Middle Aged
  • Potassium Channel Blockers / pharmacology
  • Protein Transport / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology


  • Kv1.3 Potassium Channel
  • Potassium Channel Blockers