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    
Abstract/OtherAbstract:
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.
Authors:
C Poulopoulou; Z Papadopoulou-Daifoti; A Hatzimanolis; K Fragiadaki; A Polissidis; E Anderzanova; P Davaki; C G Katsiari; P P Sfikakis
Related Documents :
7900886 - Comparison of ito in young and adult human atrial myocytes: evidence for developmental ...
11683396 - Directional movement of rat prostate cancer cells in direct-current electric field: inv...
17289936 - Identifying nonselective hits from a homogeneous calcium assay screen.
16732426 - Cell communication in taste buds.
19414266 - Dysideamine, a new sesquiterpene aminoquinone, protects hippocampal neuronal cells agai...
21750166 - Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-depend...
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    
Affiliation:
Athens University Medical School, Athens, Greece.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Female
Glutamic Acid / blood*
Humans
Kv1.3 Potassium Channel / physiology*
Lupus Erythematosus, Systemic / blood*,  metabolism*
Middle Aged
Chemical
Reg. No./Substance:
0/Kv1.3 Potassium Channel; 56-86-0/Glutamic Acid
Comments/Corrections
Comment In:
Arthritis Rheum. 2008 May;58(5):1216-9   [PMID:  18438836 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  An orally bioavailable spleen tyrosine kinase inhibitor delays disease progression and prolongs surv...
Next Document:  Correlation of magnetization transfer ratio histogram parameters with neuropsychiatric systemic lupu...