Document Detail

Glutamate levels and activity of the T cell voltage-gated potassium Kv1.3 channel in patients with systemic lupus erythematosus.
MedLine Citation:
PMID:  18438846     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Alterations in glutamate homeostasis and Kv1.3 voltage-gated potassium channel function have been independently associated with T cell dysfunction, whereas selective blockade of Kv1.3 channels inhibits T cell activation and improves T cell-mediated manifestations in animal models of autoimmunity. Because low extracellular glutamate concentrations enhance the activity of this channel in normal T cells ex vivo, we undertook this study to examine serum glutamate concentrations and Kv1.3 channel activity in patients with systemic lupus erythematosus (SLE). METHODS: We used high-performance liquid chromatography for glutamate measurements, and we used the whole-cell patch-clamp technique for electrophysiologic studies performed in freshly isolated, noncultured peripheral T cells. RESULTS: Mean +/- SD serum concentrations of glutamate were lower in patients with either clinically quiescent SLE (77 +/- 27 microM [n = 18]) or active SLE (61 +/- 36 microM [n = 16]) than in healthy controls (166 +/- 64 microM [n = 24]) (both P < 0.0001). The intrinsic gating properties of the Kv1.3 channels in lupus T cells were found to be comparable with those in healthy control-derived T cells. Notably, electrophysiologic data from SLE patient-derived T cells exposed to extracellular glutamate concentrations similar to their respective serum levels (50 microM) demonstrated Kv1.3 current responses enhanced by almost 20% (P < 0.01) compared with those subsequently obtained from the same cell in the presence of glutamate concentrations within control serum levels (200 microM). CONCLUSION: Based on the key role of Kv1.3 channel activity in lymphocyte physiology, an enhancing in vivo effect of low serum glutamate concentrations on the functional activity of this channel may contribute to lupus T cell hyperactivity. Studies to further elucidate Kv1.3 responses in SLE, as well as the possible pathogenetic role of this unsuspected metabolic abnormality, may have therapeutic implications for SLE patients.
C Poulopoulou; Z Papadopoulou-Daifoti; A Hatzimanolis; K Fragiadaki; A Polissidis; E Anderzanova; P Davaki; C G Katsiari; P P Sfikakis
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  58     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-27     Completed Date:  2008-06-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1445-50     Citation Subset:  AIM; IM    
Athens University Medical School, Athens, Greece.
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MeSH Terms
Glutamic Acid / blood*
Kv1.3 Potassium Channel / physiology*
Lupus Erythematosus, Systemic / blood*,  metabolism*
Middle Aged
Reg. No./Substance:
0/Kv1.3 Potassium Channel; 56-86-0/Glutamic Acid
Comment In:
Arthritis Rheum. 2008 May;58(5):1216-9   [PMID:  18438836 ]

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